To see the other types of publications on this topic, follow the link: Extracellular signalling molecules.
Journal articles on the topic 'Extracellular signalling molecules'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Extracellular signalling molecules.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Chen, Zhen-Ping, Andrew Levy, and Stafford L. Lightman. "Nucleotides as Extracellular Signalling Molecules." Journal of Neuroendocrinology 7, no. 2 (1995): 83–96. http://dx.doi.org/10.1111/j.1365-2826.1995.tb00671.x.
Full text
2
Gradilla, Ana-Citlali, Eléanor Simon, Gustavo Aguilar, and Isabel Guerrero. "From intra- to extracellular vesicles: extracellular vesicles in developmental signalling." Essays in Biochemistry 62, no. 2 (2018): 215–23. http://dx.doi.org/10.1042/ebc20180001.
Full textAbstract:
Signalling from cell-to-cell is fundamental for determining differentiation and patterning. This communication can occur between adjacent and distant cells. Extracellular vesicles (EVs) are membrane-based structures thought to facilitate the long-distance movement of signalling molecules. EVs have recently been found to allow the transport of two major developmental signalling pathways: Hedgehog and Wnt. These signalling molecules undergo crucial post-translational lipid modifications, which anchor them to membranes and impede their free release into the extracellular space. Preparation of these ligands in EVs involves intracellular vesicle sorting in an endocytosis-dependent recycling process before secretion. In the present review, we discuss the most recent advances with regard to EV involvement in developmental signalling at a distance. We focus on the role of the protein complexes involved in EV genesis, and provide a comprehensive perspective of the contribution of these complexes to intracellular vesicle sorting of developmental signals for their extracellular secretion, reception and transduction.
3
Giuliani, Anna Lisa, Alba Clara Sarti, and Francesco Di Virgilio. "Extracellular nucleotides and nucleosides as signalling molecules." Immunology Letters 205 (January 2019): 16–24. http://dx.doi.org/10.1016/j.imlet.2018.11.006.
Full text
4
Cantrell, D. A. "Phosphoinositide 3-kinase signalling pathways." Journal of Cell Science 114, no. 8 (2001): 1439–45. http://dx.doi.org/10.1242/jcs.114.8.1439.
Full textAbstract:
Phosphoinositide 3-kinases (PI3Ks) phosphorylate the 3′-OH position of the inositol ring of inositol phospholipids, producing three lipid products: PtdIns(3)P, PtdIns(3,4)P(2) and PtdIns(3,4,5)P(3). These lipids bind to the pleckstrin homology (PH) domains of proteins and control the activity and subcellular localisation of a diverse array of signal transduction molecules. Three major classes of signalling molecule are regulated by binding of D-3 phosphoinositides to PH domains: guanine-nucleotide-exchange proteins for Ρ family GTPases, the TEC family tyrosine kinases such as BTK and ITK in B and T lymphocytes, respectively, and the AGC superfamily of serine/threonine protein kinases. These molecules are activated by a variety of extracellular stimuli and have been implicated in a wide range of cellular processes, including cell cycle progression, cell growth, cell motility, cell adhesion and cell survival.
5
Schulze-Lohoff, E., A. Ogilvie, and R. B. Stenzel. "Extracellular nucleotides as signalling molecules for renal mesangial cells." Journal of Autonomic Pharmacology 16, no. 6 (1996): 381–84. http://dx.doi.org/10.1111/j.1474-8673.1996.tb00058.x.
Full text
6
Humphries, M. J., M. A. Travis, K. Clark, and A. P. Mould. "Mechanisms of integration of cells and extracellular matrices by integrins." Biochemical Society Transactions 32, no. 5 (2004): 822–25. http://dx.doi.org/10.1042/bst0320822.
Full textAbstract:
While it is self-evident that all extracellular molecules are an integral part of a multicellular organism, it is paradoxical that they are often considered to be dissociated from cells. The reality is that a continuum of dynamic, bi-directional interactions links the intracellular environment through cell-surface receptors to multimolecular extracellular assemblies. These interactions not only control the behaviour of individual cells, but also determine tissue architecture. Adhesion receptor function is partly determined by an ability to tether the contractile cytoskeleton to the plasma membrane, but there is also evidence that integrin receptors modulate signalling events that are essential for cellular differentiation. A major challenge is now to integrate work at the atomic, molecular and cellular levels, and obtain holistic insights into the mechanisms controlling cell adhesion. In the present study, we review current knowledge of the molecular mechanisms employed by cells to integrate with the extracellular matrix. Two main topics are covered: the adaptation of integrin structure for bi-directional signalling and the integration of integrin signalling with other receptors.
7
Santos, Jerran, Penelope V. Dalla, and Bruce K. Milthorpe. "A Molecular Analysis of Cytokine Content across Extracellular Vesicles, Secretions, and Intracellular Space from Different Site-Specific Adipose-Derived Stem Cells." International Journal of Molecular Sciences 23, no. 1 (2021): 397. http://dx.doi.org/10.3390/ijms23010397.
Full textAbstract:
Cytokines are multifunctional small proteins that have a vital influence on inflammatory states of tissues and play a role in signalling and cellular control mechanisms. Cytokine expression has primarily been viewed as a form of direct secretion of molecules through an active transportation; however, other forms of active transport such as extracellular vesicles are at play. This is particularly important in stem cells where signalling molecules are key to communication managing the levels of proliferation, migration, and differentiation into mature cells. This study investigated cytokines from intracellular content, direct cellular secretions, and extracellular vesicles from adult adipose-derived stem cells isolated from three distinct anatomical locations: abdomen, thigh, and chin. The cells were cultured investigated using live cell microscopy, cytokine assays, and bioinformatics analysis. The cytokines quantified and examined from each sample type showed a distinct difference between niche areas and sample types. The varying levels of TNF-alpha, IL-6 and IL-8 cytokines were shown to play a crucial role in signalling pathways such as MAPK, ERK1/2 and JAK-STAT in cells. On the other hand, the chemotactic cytokines IL-1rn, Eotaxin, IP-10 and MCP-1 showed the most prominent changes across extracellular vesicles with roles in noncanonical signalling. By examining the local and tangential roles of cytokines in stem cells, their roles in signalling and in regenerative mechanisms may be further understood.
8
Piccinini, A. M., and K. S. Midwood. "DAMPening Inflammation by Modulating TLR Signalling." Mediators of Inflammation 2010 (2010): 1–21. http://dx.doi.org/10.1155/2010/672395.
Full textAbstract:
Damage-associated molecular patterns (DAMPs) include endogenous intracellular molecules released by activated or necrotic cells and extracellular matrix (ECM) molecules that are upregulated upon injury or degraded following tissue damage. DAMPs are vital danger signals that alert our immune system to tissue damage upon both infectious and sterile insult. DAMP activation of Toll-like receptors (TLRs) induces inflammatory gene expression to mediate tissue repair. However, DAMPs have also been implicated in diseases where excessive inflammation plays a key role in pathogenesis, including rheumatoid arthritis (RA), cancer, and atherosclerosis. TLR activation by DAMPs may initiate positive feedback loops where increasing tissue damage perpetuates pro-inflammatory responses leading to chronic inflammation. Here we explore the current knowledge about distinct signalling cascades resulting from self TLR activation. We also discuss the involvement of endogenous TLR activators in disease and highlight how specifically targeting DAMPs may yield therapies that do not globally suppress the immune system.
9
Sultan, Salma, Walid Mottawea, JuDong Yeo, and Riadh Hammami. "Gut Microbiota Extracellular Vesicles as Signaling Molecules Mediating Host-Microbiota Communications." International Journal of Molecular Sciences 22, no. 23 (2021): 13166. http://dx.doi.org/10.3390/ijms222313166.
Full textAbstract:
Over the past decade, gut microbiota dysbiosis has been linked to many health disorders; however, the detailed mechanism of this correlation remains unclear. Gut microbiota can communicate with the host through immunological or metabolic signalling. Recently, microbiota-released extracellular vesicles (MEVs) have emerged as significant mediators in the intercellular signalling mechanism that could be an integral part of microbiota-host communications. MEVs are small membrane-bound vesicles that encase a broad spectrum of biologically active compounds (i.e., proteins, mRNA, miRNA, DNA, carbohydrates, and lipids), thus mediating the horizontal transfer of their cargo across intra- and intercellular space. In this study, we provide a comprehensive and in-depth discussion of the biogenesis of microbial-derived EVs, their classification and routes of production, as well as their role in inter-bacterial and inter-kingdom signaling.
10
Wilson, C., N. Vereshchagina, B. Reynolds, D. Meredith, C. A. R. Boyd, and D. C. I. Goberdhan. "Extracellular and subcellular regulation of the PI3K/Akt cassette: new mechanisms for controlling insulin and growth factor signalling." Biochemical Society Transactions 35, no. 2 (2007): 219–21. http://dx.doi.org/10.1042/bst0350219.
Full textAbstract:
The PI3K (phosphoinositide 3-kinase)/Akt (also called protein kinase B) signalling cassette plays a central role in the response to growth factors, particularly insulin-like molecules, and its misregulation is a characteristic feature of diabetes and many forms of human cancer. Recent molecular genetic studies initiated in the fruitfly, Drosophila melanogaster, have highlighted two new cell-type-specific mechanisms regulating PI3K/Akt signalling and its downstream effects. First, the cellular response to this cassette is modulated by several classes of cell-surface transporters and sensors, suggesting an important role for extracellular nutrients in insulin-sensitivity. Secondly, various cell types show a markedly different subcellular distribution of the activated kinase Akt, influencing the cellular functions of this molecule. These findings reveal new mechanisms by which processes such as growth, lipogenesis and insulin resistance can be differentially regulated and may suggest novel strategies for treating insulin-linked diseases.
11
Kim, Soo-Hyun, Jeremy Turnbull, and Scott Guimond. "Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor." Journal of Endocrinology 209, no. 2 (2011): 139–51. http://dx.doi.org/10.1530/joe-10-0377.
Full textAbstract:
Extracellular matrices (ECM) are secreted molecules that constitute the cell microenvironment, composed of a dynamic and complex array of glycoproteins, collagens, glycosaminoglycans and proteoglycans. ECM provides the bulk, shape and strength of many tissues in vivo, such as basement membrane, bone and cartilage. In vitro, most animal cells can only grow when they are attached to surfaces through ECM. ECM is also the substrate for cell migration. However, ECM provides much more than just mechanical and structural support, with implications in developmental patterning, stem cell niches and cancer. ECM imparts spatial context for signalling events by various cell surface growth factor receptors and adhesion molecules such as integrins. The external physical properties of ECM may also have a role in the signalling process. ECM molecules can be flexible and extendable, and mechanical tension can expose cryptic sites, which could further interact with growth factors or their receptors. ECM proteins and structures can determine the cell behaviour, polarity, migration, differentiation, proliferation and survival by communicating with the intracellular cytoskeleton and transmission of growth factor signals. Integrins and proteoglycans are the major ECM adhesion receptors which cooperate in signalling events, determining the signalling outcomes, and thus the cell fate. This review focuses on the emerging concept of spatial cell biology of ECM, especially the current understanding of integrins and heparan sulphate proteoglycans as the essential cellular machineries that sense, integrate and respond to the physical and chemical environmental information either by directly connecting with the local adhesion sites or by regulating global cellular processes through growth factor receptor signalling pathways, leading to the integration of both external and internal signals in space and time.
12
Davies, Kerry J. "Methods of Cell Propulsion through the Local Stroma in Breast Cancer." International Journal of Breast Cancer 2014 (2014): 1–6. http://dx.doi.org/10.1155/2014/197480.
Full textAbstract:
In the normal breast, cellular structures change cyclically in response to ovarian hormones. Cell proliferation, apoptosis, invasion, and differentiation are integral processes that are precisely regulated. Normal epithelial cells depend on the formation of intercellular adhesion contacts to form a continuous sheet of stratifying cell layers that are attached to one and other horizontally and vertically. Cells migrate by extending membrane protrusions to explore the extracellular space locating their targets in a chemotactic manner. The formation of cell protrusions is driven by the assembly of actin filaments at the leading edge. Reorganisation is regulated by a highly integrated signalling cascade that transduces extracellular stimuli to the actin filaments. This signalling cascade is governed by GTPases which act as molecular switches leading to actin polymerisation and the formation of filopodia and lamellipodia. This process is linked to downstream molecules known collectively as WASP proteins, which, in the presence of cortactin, form a complex leading to nucleation and formation of branched filaments. In breast cancer, the cortactin is over expressed leading to increased cellular motility and invasiveness. This hugely complex and integrated signalling cascade transduces extracellular stimuli. There are multiple genes related to cell motility which are dysregulated in human breast cancers.
13
Petrich, Brian. "Talin-dependent integrin signalling in vivo." Thrombosis and Haemostasis 101, no. 06 (2009): 1020–24. http://dx.doi.org/10.1160/th08-08-0553.
Full textAbstract:
SummaryIntegrins are heterodimeric adhesion receptors essential for metazoan life. In addition to mediating cell-extracellular matrix and cell-cell interactions, integrins are bona fide signalling receptors in that they transmit information in both directions across the plasma membrane. The affinity of integrins for extracellular ligands is regulated through a process termed integrin activation or “inside-out signalling”. On the other hand, ligand binding to integrins can induce the recruitment and activation of a number of enzymes and adaptors such as pp125FAK and Src family kinases, to initiate “outside-in signalling”. Intensive investigation into the mechanisms of integrin signalling has revealed many of the key players; amongst these, one of the most important is talin. Our understanding of how many of these molecules interact is now understood at the atomic level thanks to detailed structural studies. Indeed structural information and model cell systems have provided unique opportunities to dissect the molecular mechanisms of many aspects of integrin signalling. Recent studies have begun testing the biological significance of these mechanisms using in-vivo models, particular genetically modified mice. The generation and characterisation of in-vivo models to study integrin signalling has provided valuable information into the functional significance of integrin signalling in fundamental physiological processes as well as within the context of human disease. Here, I will review recent insights that have been gained into integrin signalling through the use of genetically modified mice focusing on integrin αIIbβ3 (GPIIb-IIIa) and the regulation of its function in haemostasis and thrombosis.
14
Kubota, Satoshi, and Masaharu Takigawa. "Cellular and molecular actions of CCN2/CTGF and its role under physiological and pathological conditions." Clinical Science 128, no. 3 (2014): 181–96. http://dx.doi.org/10.1042/cs20140264.
Full textAbstract:
CCN family protein 2 (CCN2), also widely known as connective tissue growth factor (CTGF), is one of the founding members of the CCN family of matricellular proteins. Extensive investigation on CCN2 over decades has revealed the novel molecular action and functional properties of this unique signalling modulator. By its interaction with multiple molecular counterparts, CCN2 yields highly diverse and context-dependent biological outcomes in a variety of microenvironments. Nowadays, CCN2 is recognized to conduct the harmonized development of relevant tissues, such as cartilage and bone, in the skeletal system, by manipulating extracellular signalling molecules involved therein by acting as a hub through a web. However, on the other hand, CCN2 occasionally plays profound roles in major human biological disorders, including fibrosis and malignancies in major organs and tissues, by modulating the actions of key molecules involved in these clinical entities. In this review, the physiological and pathological roles of this unique protein are comprehensively summarized from a molecular network-based viewpoint of CCN2 functionalities.
15
Zhou, Feng-Quan, and William D. Snider. "Intracellular control of developmental and regenerative axon growth." Philosophical Transactions of the Royal Society B: Biological Sciences 361, no. 1473 (2006): 1575–92. http://dx.doi.org/10.1098/rstb.2006.1882.
Full textAbstract:
Axon growth is a highly regulated process that requires stimulating signals from extracellular factors. The extracellular signals are then transduced to regulate coordinately gene expression and local axon assembly. Growth factors, especially neurotrophins that act via receptor tyrosine kinases, have been heavily studied as extracellular factors that stimulate axon growth. Downstream of receptor tyrosine kinases, recent studies have suggested that phosphatidylinositol-3 kinase (PI3K) regulates local assembly of axonal cytoskeleton, especially microtubules, via glycogen synthase kinase 3β (GSK-3β) and multiple microtubule binding proteins. The role of extracellular signal regulated kinase (ERK) signalling in regulation of local axon assembly is less clear, but may involve the regulation of local protein translation. Gene expression during axon growth is regulated by transcription factors, among which cyclic AMP response element binding protein and nuclear factors of activated T-cells (NFATs) are known to be required for neurotrophin (NT)-induced axon extension. In addition to growth factors, extracellular matrix molecules and neuronal activity contribute importantly to control axon growth. Increasingly, evidence suggests that these influences act to enhance growth via coordinating with growth factor signalling. Finally, evidence is emerging that developmental versus regenerative axon growth may be mediated by distinct signalling pathways, both at the level of gene transcription and at the level of local axon assembly.
16
Angst, B. D., C. Marcozzi, and A. I. Magee. "The cadherin superfamily: diversity in form and function." Journal of Cell Science 114, no. 4 (2001): 629–41. http://dx.doi.org/10.1242/jcs.114.4.629.
Full textAbstract:
Over recent years cadherins have emerged as a growing superfamily of molecules, and a complex picture of their structure and their biological functions is becoming apparent. Variation in their extracellular region leads to the large potential for recognition properties of this superfamily. This is demonstrated strikingly by the recently discovered FYN-binding CNR-protocadherins; these exhibit alternative expression of the extracellular portion, which could lead to distinct cell recognition in different neuronal populations, whereas their cytoplasmic part, and therefore intracellular interactions, is constant. Diversity in the cytoplasmic moiety of the cadherins imparts specificity to their interactions with cytoplasmic components; for example, classical cadherins interact with catenins and the actin filament network, desmosomal cadherins interact with catenins and the intermediate filament system and CNR-cadherins interact with the SRC-family kinase FYN. Recent evidence suggests that CNR-cadherins, 7TM-cadherins and T-cadherin, which is tethered to the membrane by a GPI anchor, all localise to lipid rafts, specialised cell membrane domains rich in signalling molecules. Originally thought of as cell adhesion molecules, cadherin superfamily molecules are now known to be involved in many biological processes, such as cell recognition, cell signalling, cell communication, morphogenesis, angiogenesis and possibly even neurotransmission.
17
Urano, Daisuke, Jin-Gui Chen, José Ramón Botella, and Alan M. Jones. "Heterotrimeric G protein signalling in the plant kingdom." Open Biology 3, no. 3 (2013): 120186. http://dx.doi.org/10.1098/rsob.120186.
Full textAbstract:
In animals, heterotrimeric G proteins, comprising α-, β-and γ-subunits, perceive extracellular stimuli through cell surface receptors, and transmit signals to ion channels, enzymes and other effector proteins to affect numerous cellular behaviours. In plants, G proteins have structural similarities to the corresponding molecules in animals but transmit signals by atypical mechanisms and effector proteins to control growth, cell proliferation, defence, stomate movements, channel regulation, sugar sensing and some hormonal responses. In this review, we summarize the current knowledge on the molecular regulation of plant G proteins, their effectors and the physiological functions studied mainly in two model organisms: Arabidopsis thaliana and rice ( Oryza sativa ). We also look at recent progress on structural analyses, systems biology and evolutionary studies.
18
Smith, J. C., A. Hagemann, Y. Saka, and P. H. Williams. "Understanding how morphogens work." Philosophical Transactions of the Royal Society B: Biological Sciences 363, no. 1495 (2008): 1387–92. http://dx.doi.org/10.1098/rstb.2007.2256.
Full textAbstract:
In this article, we describe the mechanisms by which morphogens in the Xenopus embryo exert their long-range effects. Our results are consistent with the idea that signalling molecules such as activin and the nodal-related proteins traverse responding tissue not by transcytosis or by cytonemes but by movement through the extracellular space. We suggest, however, that additional experiments, involving real-time imaging of morphogens, are required for a real understanding of what influences signalling range and the shape of a morphogen gradient.
19
Morris, M. B., N. Hamra, A. C. Lonic, and F. Felquer. "182. NOVEL SIGNALLING IN MOUSE EMBRYONIC STEM CELLS GENERATES PRIMITIVE ECTODERM-LIKE CELLS." Reproduction, Fertility and Development 21, no. 9 (2009): 100. http://dx.doi.org/10.1071/srb09abs182.
Full textAbstract:
The phenotypic status of embryonic stem (ES) cells is controlled in part by signalling pathways which translate inputs mediated by extracellular molecules. An important extracellular protagonist in mouse ES cells is LIF (leukaemia inhibitory factor) which interacts with the gp130–LIFR receptor complex to activate a number of downstream signalling pathways, including the STAT3, MEK/ERK and PI3K/Akt. These pathways, together with others, interact in complex and sometimes competing ways to generate the well-known characteristics of mouse ES cells of self-renewal, high rates of proliferation, and pluripotence. The addition of a second molecule, L-proline, to the extracellular environment alters the pluripotent status of mouse ES cells, converting them to a second pluripotent population equivalent to the primitive ectoderm of the pre-gastrulating embryo. This conversion, from ES cells to primitive ectoderm-like cells, primes the latter for directed differentiation to specific cell types (1). Here we show, using inhibitor studies and kinome array analysis, that this small molecule appears to work by (i) changing the balance in activity of signalling pathways already stimulated by LIF and (ii) activating additional signalling pathways. Specifically, L-proline rapidly further activates the LIF-stimulated MEK/ERK pathway, tipping the balance in favour of primitive-ectoderm formation and away from ES-cell self-renewal sustained by LIF-mediated activation of the STAT3 pathway. In addition, L-proline rapidly stimulates other pathways including p38, mTOR and PI3K/Akt each of which contributes, to a greater or lesser extent, to the conversion to primitive ectoderm-like cells. These results indicate that (i) L-proline acts in novel ways to stimulate embryo-like developmental progression in ES cells and (ii) through the addition of small, nontoxic activators and inhibitors of signalling pathways, the differentiation of pluripotent ES cells might be controlled sufficiently well for the homogeneous production of specific cell types suitable for use in animal models of human disease.
20
Htet, Myo, Jane E. Nally, Patricia E. Martin, and Yvonne Dempsie. "New Insights into Pulmonary Hypertension: A Role for Connexin-Mediated Signalling." International Journal of Molecular Sciences 23, no. 1 (2021): 379. http://dx.doi.org/10.3390/ijms23010379.
Full textAbstract:
Pulmonary hypertension is a serious clinical condition characterised by increased pulmonary arterial pressure. This can lead to right ventricular failure which can be fatal. Connexins are gap junction-forming membrane proteins which serve to exchange small molecules of less than 1 kD between cells. Connexins can also form hemi-channels connecting the intracellular and extracellular environments. Hemi-channels can mediate adenosine triphosphate release and are involved in autocrine and paracrine signalling. Recently, our group and others have identified evidence that connexin-mediated signalling may be involved in the pathogenesis of pulmonary hypertension. In this review, we discuss the evidence that dysregulated connexin-mediated signalling is associated with pulmonary hypertension.
21
Zampieri, N., and M. V. Chao. "Mechanisms of neurotrophin receptor signalling." Biochemical Society Transactions 34, no. 4 (2006): 607–11. http://dx.doi.org/10.1042/bst0340607.
Full textAbstract:
Regulation of cell survival decisions and neuronal plasticity by neurotrophins are mediated by two classes of receptors, Trks (tropomyosin receptor kinases) and p75, the first discovered member of the tumour necrosis factor receptor superfamily. The p75 receptor participates with the TrkA receptor in the formation of high-affinity nerve growth factor-binding sites to promote survival under limiting concentrations of neurotrophins. Activation of Trk receptors leads to increased phosphorylation of Shc (Src homology and collagen homology), phospholipase C-γ and novel adaptor molecules, such as the ARMS (ankyrin-rich membrane spanning)/Kidins220 protein. Small ligands that interact with G-protein-coupled receptors can also activate Trk receptor kinase activity. Transactivation of Trk receptors and their downstream signalling pathways raise the possibility of using small molecules to elicit neuroprotective effects for the treatment of neurodegenerative diseases. Like amyloid precursor protein and Notch, p75 is a substrate for γ-secretase cleavage. The p75 receptor undergoes an α-secretase-mediated release of the extracellular domain followed by a γ-secretase-mediated intramembrane cleavage. Cleavage of p75 may represent a general mechanism for transmitting signals as an independent receptor and as a co-receptor for other signalling systems.
22
Betti, Federico, Maria Jose Ladera-Carmona, Daan A. Weits, et al. "Exogenous miRNAs induce post-transcriptional gene silencing in plants." Nature Plants 7, no. 10 (2021): 1379–88. http://dx.doi.org/10.1038/s41477-021-01005-w.
Full textAbstract:
AbstractPlants seem to take up exogenous RNA that was artificially designed to target specific genes, followed by activation of the RNA interference (RNAi) machinery. It is, however, not known whether plants use RNAs themselves as signalling molecules in plant-to-plant communication, other than evidence that an exchange of small RNAs occurs between parasitic plants and their hosts. Exogenous RNAs from the environment, if taken up by some living organisms, can indeed induce RNAi. This phenomenon has been observed in nematodes and insects, and host Arabidopsis cells secrete exosome-like extracellular vesicles to deliver plant small RNAs into Botrytis cinerea. Here we show that micro-RNAs (miRNAs) produced by plants act as signalling molecules affecting gene expression in other, nearby plants. Exogenous miRNAs, such as miR156 and miR399, trigger RNAi via a mechanism requiring both AGO1 and RDR6. This emphasizes that the production of secondary small interfering RNAs is required. This evidence highlights the existence of a mechanism in which miRNAs represent signalling molecules that enable communication between plants.
23
White, Joni Renee, Priscila Dauros-Singorenko, Jiwon Hong, Frédérique Vanholsbeeck, Anthony Phillips, and Simon Swift. "The complex, bidirectional role of extracellular vesicles in infection." Biochemical Society Transactions 49, no. 2 (2021): 881–91. http://dx.doi.org/10.1042/bst20200788.
Full textAbstract:
Cells from all domains of life release extracellular vesicles (EVs), packages that carry a cargo of molecules that participate in communication, co-ordination of population behaviours, virulence and immune response mechanisms. Mammalian EVs play an increasingly recognised role to fight infection, yet may also be commandeered to disseminate pathogens and enhance infection. EVs released by bacterial pathogens may deliver toxins to host cells, signalling molecules and new DNA to other bacteria, and act as decoys, protecting infecting bacteria from immune killing. In this review, we explore the role of EVs in infection from the perspective of both the pathogen and host, and highlight their importance in the host/pathogen relationship. We highlight proposed strategies for EVs in therapeutics, and call attention to areas where existing knowledge and evidence is lacking.
24
Stein, Paula, Virginia Savy, Audrey M. Williams, and Carmen J. Williams. "Modulators of calcium signalling at fertilization." Open Biology 10, no. 7 (2020): 200118. http://dx.doi.org/10.1098/rsob.200118.
Full textAbstract:
Calcium (Ca 2+ ) signals initiate egg activation across the animal kingdom and in at least some plants. These signals are crucial for the success of development and, in the case of mammals, health of the offspring. The mechanisms associated with fertilization that trigger these signals and the molecules that regulate their characteristic patterns vary widely. With few exceptions, a major contributor to fertilization-induced elevation in cytoplasmic Ca 2+ is release from endoplasmic reticulum stores through the IP3 receptor. In some cases, Ca 2+ influx from the extracellular space and/or release from alternative intracellular stores contribute to the rise in cytoplasmic Ca 2+ . Following the Ca 2+ rise, the reuptake of Ca 2+ into intracellular stores or efflux of Ca 2+ out of the egg drive the return of cytoplasmic Ca 2+ back to baseline levels. The molecular mediators of these Ca 2+ fluxes in different organisms include Ca 2+ release channels, uptake channels, exchangers and pumps. The functions of these mediators are regulated by their particular activating mechanisms but also by alterations in their expression and spatial organization. We discuss here the molecular basis for modulation of Ca 2+ signalling at fertilization, highlighting differences across several animal phyla, and we mention key areas where questions remain.
25
Melzer, Michaela, Susanna Schubert, Simon Franz Müller та ін. "Rho/ROCK Inhibition Promotes TGF-β3-Induced Tenogenic Differentiation in Mesenchymal Stromal Cells". Stem Cells International 2021 (8 жовтня 2021): 1–11. http://dx.doi.org/10.1155/2021/8284690.
Full textAbstract:
Mesenchymal stromal cells (MSC) represent a promising therapeutic tool for tendon regeneration. Their tenogenic differentiation is crucial for tissue engineering approaches and may support their beneficial effects after cell transplantation in vivo. The transforming growth factor (TGF)-β, signalling via intracellular Smad molecules, is a potent paracrine mediator of tenogenic induction. Moreover, scaffold topography or tendon matrix components induced tenogenesis via activation of the Rho/ROCK cascade, which, however, is also involved in pathological adaptations in extracellular matrix pathologies. The aim of this study was to investigate the interplay of Rho/ROCK and TGF-β3/Smad signalling in tenogenic differentiation in both human and equine MSC. Primary equine and human MSC isolated from adipose tissue were cultured as monolayers or on tendon-derived decellularized scaffolds to evaluate the influence of the ROCK inhibitor Y-27632 on TGF-β3-induced tenogenic differentiation. The MSC were incubated with and without TGF-β3 (10 ng/ml), Y-27632 (10 μM), or both. On day 1 and day 3, the signalling pathway of TGF-β and the actin cytoskeleton were visualized by Smad 2/3 and phalloidin staining, and gene expression of signalling molecules and tendon markers was assessed. ROCK inhibition was confirmed by disruption of the actin cytoskeleton. Activation of Smad 2/3 with nuclear translocation was evident upon TGF-β3 stimulation. Interestingly, this effect was most pronounced with additional ROCK inhibition in both species ( p < 0.05 in equine MSC). In line with that, the tendon marker scleraxis showed the strongest upregulation when TGF-β3 and ROCK inhibition were combined ( p < 0.05 in human MSC). The regulation pattern of tendon extracellular matrix components and the signalling molecules TGF-β3 and Smad 8 showed differences between human and equine MSC. The obtained results showed that ROCK inhibition promotes the TGF-β3/Smad 2/3 axis, with possible implications for future MSC priming regimes in tendon therapy.
26
Akira, S., M. Yamamoto, and K. Takeda. "Role of adapters in Toll-like receptor signalling." Biochemical Society Transactions 31, no. 3 (2003): 637–42. http://dx.doi.org/10.1042/bst0310637.
Full textAbstract:
Toll-like receptors (TLRs) play a critical role in the detection of invading pathogens within the body and the subsequent immune response. Individual TLRs recognize distinct microbial components. The TLRs are a type 1 transmembrane receptor that possess an extracellular leucine-rich repeat domain and cytoplasmic domain homologous with that of the interleukin 1 receptor (IL-1R) family. Upon stimulation, TLR recruits the IL-1R-associated kinase (IRAK) via the adapter MyD88, ultimately leading to the activation of nuclear factor-κB. Cytokine production in response to all TLR ligands is completely abolished in MyD88-deficient cells, indicating that MyD88 is an essential signalling molecule shared among members of the IL-1R/Toll family. However, several novel adaptor molecules have recently been identified. Evidence is now accumulating showing that differential utilization of these adaptors may activate overlapping as well as distinct signalling pathways, and ultimately give rise to distinct biological effects exerted by individual TLR family members.
27
Kleinbongard, P., and G. Heusch. "Extracellular signalling molecules in the ischaemic/reperfused heart - druggable and translatable for cardioprotection?" British Journal of Pharmacology 172, no. 8 (2014): 2010–25. http://dx.doi.org/10.1111/bph.12902.
Full text
28
Raimondi, Claudio. "Neuropilin-1 enforces extracellular matrix signalling via ABL1 to promote angiogenesis." Biochemical Society Transactions 42, no. 5 (2014): 1429–34. http://dx.doi.org/10.1042/bst20140141.
Full textAbstract:
Neuropilin-1 (NRP1), together with neuropilin-2, belongs to the neuropilin family. Neuropilins are transmembrane proteins essential for vascular and neural development and act as co-receptors for secreted signalling molecules of the class 3 semaphorin and vascular endothelial growth factor A (VEGF-A) families. NRP1 promotes VEGF-A signal in blood vascular endothelium and semaphorin signal in lymphatic endothelium, by forming complexes with its co-receptors. Mouse mutant studies established that NRP1 expression is essential during development because mice lacking NRP1 expression die embryonically and show severe neuronal and cardiovascular defects. Even though the contribution of NRP1 to vascular development has been mainly ascribed to its function as a VEGF-A receptor, recent evidence suggests that NRP1 contributes to angiogenesis through VEGF-independent mechanisms. In the present paper, we provide an overview of NRP1 functions in the vasculature and discuss current knowledge of NRP1-dependent signalling in the endothelium.
29
Pankratova, Maria D., Andrei A. Riabinin, Elizaveta A. Butova, et al. "YAP/TAZ Signalling Controls Epidermal Keratinocyte Fate." International Journal of Molecular Sciences 25, no. 23 (2024): 12903. https://doi.org/10.3390/ijms252312903.
Full textAbstract:
The paralogues Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) control cell proliferation and cell fate determination from embryogenesis to ageing. In the skin epidermis, these proteins are involved in both homeostatic cell renewal and injury-induced regeneration and also drive carcinogenesis and other pathologies. YAP and TAZ are usually considered downstream of the Hippo pathway. However, they are the central integrating link for the signalling microenvironment since they are involved in the interplay with signalling cascades induced by growth factors, cytokines, and physical parameters of the extracellular matrix. In this review, we summarise the evidence on how YAP and TAZ are activated in epidermal keratinocytes; how YAP/TAZ-mediated signalling cooperates with other signalling molecules at the plasma membrane, cytoplasmic, and nuclear levels; and how YAP/TAZ ultimately controls transcription programmes, defining epidermal cell fate.
30
Shankar, Jay, Cecile Boscher, and Ivan R. Nabi. "Caveolin-1, galectin-3 and lipid raft domains in cancer cell signalling." Essays in Biochemistry 57 (February 6, 2015): 189–201. http://dx.doi.org/10.1042/bse0570189.
Full textAbstract:
Spatial organization of the plasma membrane is an essential feature of the cellular response to external stimuli. Receptor organization at the cell surface mediates transmission of extracellular stimuli to intracellular signalling molecules and effectors that impact various cellular processes including cell differentiation, metabolism, growth, migration and apoptosis. Membrane domains include morphologically distinct plasma membrane invaginations such as clathrin-coated pits and caveolae, but also less well-defined domains such as lipid rafts and the galectin lattice. In the present chapter, we will discuss interaction between caveolae, lipid rafts and the galectin lattice in the control of cancer cell signalling.
31
Kaiser, Karol, and Vitezslav Bryja. "Choroid Plexus: The Orchestrator of Long-Range Signalling Within the CNS." International Journal of Molecular Sciences 21, no. 13 (2020): 4760. http://dx.doi.org/10.3390/ijms21134760.
Full textAbstract:
Cerebrospinal fluid (CSF) is the liquid that fills the brain ventricles. CSF represents not only a mechanical brain protection but also a rich source of signalling factors modulating diverse processes during brain development and adulthood. The choroid plexus (CP) is a major source of CSF and as such it has recently emerged as an important mediator of extracellular signalling within the brain. Growing interest in the CP revealed its capacity to release a broad variety of bioactive molecules that, via CSF, regulate processes across the whole central nervous system (CNS). Moreover, CP has been also recognized as a sensor, responding to altered composition of CSF associated with changes in the patterns of CNS activity. In this review, we summarize the recent advances in our understanding of the CP as a signalling centre that mediates long-range communication in the CNS. By providing a detailed account of the CP secretory repertoire, we describe how the CP contributes to the regulation of the extracellular environment—in the context of both the embryonal as well as the adult CNS. We highlight the role of the CP as an important regulator of CNS function that acts via CSF-mediated signalling. Further studies of CP–CSF signalling hold the potential to provide key insights into the biology of the CNS, with implications for better understanding and treatment of neuropathological conditions.
32
Zhang, Guang-Zhi, Lei Li, Zhang-Bin Luo, Cang-Yu Zhang, Yong-Gang Wang, and Xue-Wen Kang. "Identification and experimental validation of key extracellular proteins as potential targets in intervertebral disc degeneration." Bone & Joint Research 12, no. 9 (2023): 522–35. http://dx.doi.org/10.1302/2046-3758.129.bjr-2022-0369.r2.
Full textAbstract:
AimsThis study aimed, through bioinformatics analysis and in vitro experiment validation, to identify the key extracellular proteins of intervertebral disc degeneration (IDD).MethodsThe gene expression profile of GSE23130 was downloaded from the Gene Expression Omnibus (GEO) database. Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases, and we used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to analyze the functions and pathways of EP-DEGs. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and identify hub EP-DEGs. NetworkAnalyst was used to analyze transcription factors (TFs) and microRNAs (miRNAs) that regulate hub EP-DEGs. A search of the Drug Signatures Database (DSigDB) for hub EP-DEGs revealed multiple drug molecules and drug-target interactions.ResultsA total of 56 EP-DEGs were identified in the differential expression analysis. EP-DEGs were enriched in the extracellular structure organization, ageing, collagen-activated signalling pathway, PI3K-Akt signalling pathway, and AGE-RAGE signalling pathway. PPI network analysis showed that the top ten hub EP-DEGs are closely related to IDD. Correlation analysis also demonstrated a significant correlation between the ten hub EP-DEGs (p＜0.05), which were selected to construct TF–gene interaction and TF–miRNA coregulatory networks. In addition, ten candidate drugs were screened for the treatment of IDD.ConclusionThe findings clarify the roles of extracellular proteins in IDD and highlight their potential as promising novel therapeutic targets.Cite this article: Bone Joint Res 2023;12(9):522–535.
33
Rowbury, Robin J. "Intracellular and Extracellular Components as Bacterial Thermometers, and Early Warning against Thermal Stress." Science Progress 88, no. 2 (2005): 71–99. http://dx.doi.org/10.3184/003685005783238426.
Full textAbstract:
Responses induced by cold or heat are triggered following detection of temperature changes by specific sensing molecules, complexes or structures. Low temperature responses are often induced following sensing of cold-induced falls in membrane fluidity, such changes turning-on or -off enzymic activities in membrane proteins, although ribosomes and DNA may also function in cold perception. Many thermal sensors are components of structures damaged by the heat, with sensing involving changes to ribosomes, DNA, intracellular proteins and, less commonly, membrane fluidity. Additionally, secreted proteins (extracellular sensing components, ESCs) detect temperature increases i.e. act as thermometers, with ESC activation in the medium, by the stimulus, converting such sensors to extracellular signalling molecules, the extracellular induction components (EICs), which induce thermal responses. Several ESC/EIC pairs trigger thermal responses, and have the unique property of giving early warning of the stress by diffusing to regions (and organisms) not yet exposed to elevated temperatures.
34
Manson, M. M., K. A. Holloway, L. M. Howells, et al. "Modulation of signal-transduction pathways by chemopreventive agents." Biochemical Society Transactions 28, no. 2 (2000): 7–12. http://dx.doi.org/10.1042/bst0280007.
Full textAbstract:
For a disease such as cancer, where a number of alterations to normal cell function accumulate over time, there are several opportunities to inhibit, slow down or even reverse the process. Many of the changes which drive the disease process occur in cell-signalling pathways that regulate proliferation and apoptosis. As our knowledge of these complicated signalling networks improves, it is becoming clear that many molecules, both drugs and naturally occurring dietary constituents, can interact beneficially with deregulated pathways. Aspirin and other non-steroidal anti-inflammatory drugs, as well as natural compounds present in plants such as green vegetables and tea, can modulate signalling by affecting kinase activity and therefore phosphorylation of key molecules. Examples of pathways which can be modulated by these agents include activation of the transcription factor nuclear factor κB by tumour promoters or cytokines, signalling by growth factors through the growth-factor receptor/extracellular-regulated protein kinase pathways and by a number of other molecules through the stress-activated c-Jun N-terminal kinase and p38 pathways. These mitogen-activated protein kinase pathways regulate a number of transcription factors including c-Fos and c-Jun. Evidence exists, at least from in vitro experiments, that by targeting such pathways, certain dietary compounds may be able to restore abnormal rates of apoptosis and proliferation to more normal levels.
35
Fedorin, Dmitriy N., Viktoria O. Chuikova, and Alexander T. Eprintsev. "Isolation of extracellular vesicles from corn leaves using differential ultracentrifugation and the identification of miR165a microRNA." Сорбционные и хроматографические процессы 24, no. 1 (2024): 139–46. http://dx.doi.org/10.17308/sorpchrom.2024.24/12027.
Full textAbstract:
MicroRNAs are a class of non-coding RNA molecules that act as important regulators of various biological processes in plants. MicroRNAs play a significant regulatory role in the early reaction of the cell to a stressful impact, including intercellular signalling. Extracellular vesicles of plants are essential for the transport of molecules in plants. Numerous methods for isolating extracellular vesicles have been developed over the past decade, and differential centrifugation allows the isolation of small vesicles. Using the differential centrifugation method, we managed to isolate two fractions of extracellular vesicles (P40 and P100) from corn leaves that were different in size and molecular weight. The fraction of large vesicles had a size of more than 150 nm and contained high and low molecular nucleic acids. We also determined the sizes of vesicles of the P100 fraction which contained only low molecular nucleic acids: they were from 30 to 200 nm. A specific probe was designed to identify miR165a microRNA using polymerase chain reaction. Using the stem-loop probe allowed obtaining cDNA matrices larger than 70 nucleotide pairs (bp), which was sufficient to evaluate the polymerase chain reaction (PCR). The results of RT-PCR analysis with specific primers for miR165a microRNA showed the presence of an amplification product approximately 70-80 nucleotide pairs in size, which corresponded to theoretical values. Therefore, fractions of extracellular vesicle from corn leaves contained miR165a microRNA, which may explain their physiological function as intercellular transport of small non-coding RNAs.
36
Mason, MD, R. Allman, and M. Quibell. "Adhesion Molecules in Melanoma—More than Just Superglue?" Journal of the Royal Society of Medicine 89, no. 7 (1996): 393–95. http://dx.doi.org/10.1177/014107689608900710.
Full textAbstract:
Malignant melanoma is increasing in incidence, and, though early lesions are readily treatable, systemic therapy for metastatic disease remains disappointing. Integrins are a family of cell-surface molecules that mediate adhesion between the cell and the extracellular matrix. One member of the integrin family, the αvβ3 integrin, is associated with progression of melanomas, in that the most malignant cells express the highest levels of αvβ3. Like many members of the integrin family, αvβ3 recognizes the sequence Arg-Gly-Asp (RGD) in its ligands, and other molecules that contain this sequence will compete with the natural ligands (such as vitronectin) for binding. There is growing evidence that integrins function as receptors for signal transduction, and that integrin-mediated signalling can affect cell behaviour and even cell survival. Under certain circumstances, loss of integrin-mediated signalling will induce apoptosis, or programmed cell death, and we have demonstrated that melanoma cells treated with a cyclic peptide with high affinity for the αvβ3 integrin will undergo apoptosis within three days. This mechanism might be exploited therapeutically.
37
Ramesh, Divya, Shankar Bakkannavar, Vinutha R. Bhat, and Krishna Sharan. "Extracellular vesicles as novel drug delivery systems to target cancer and other diseases: Recent advancements and future perspectives." F1000Research 12 (March 23, 2023): 329. http://dx.doi.org/10.12688/f1000research.132186.1.
Full textAbstract:
Extracellular vesicles (EVs) are lipid-bound vesicles produced into the extracellular space by cells. Apoptotic bodies (ApoBD), microvesicles (MVs), and exosomes are examples of EVs, which act as essential regulators in cell-cell communication in both normal and diseased conditions. Natural cargo molecules such as miRNA, messenger RNA, and proteins are carried by EVs and transferred to nearby cells or distant cells through the process of circulation. Different signalling cascades are then influenced by these functionally active molecules. The information to be delivered to the target cells depends on the substances within the EVs that also includes synthesis method. EVs have attracted interest as potential delivery vehicles for therapies due to their features such as improved circulation stability, biocompatibility, reduced immunogenicity, and toxicity. Therefore, EVs are being regarded as potent carriers of therapeutics that can be used as a therapeutic agent for diseases like cancer. This review focuses on the exosome-mediated drug delivery to cancer cells and the advantages and challenges of using exosomes as a carrier molecule.
38
Janda, Claudia Y., and K. Christopher Garcia. "Wnt acylation and its functional implication in Wnt signalling regulation." Biochemical Society Transactions 43, no. 2 (2015): 211–16. http://dx.doi.org/10.1042/bst20140249.
Full textAbstract:
Wnt proteins are conserved signalling molecules that have an essential role in regulating diverse processes during embryogenesis and adult tissue homoeostasis. Wnts are post-translationally modified by palmitoylation, which is essential for Wnt secretion and function. Intriguingly, the crystal structure of XWnt8 in complex with the extracellular domain of the Frizzled 8 cysteine-rich domain (Fzd8-CRD) revealed that Wnts use the fatty acid as a ‘hotspot’ residue to engage its receptor, which is a unique mode of receptor-ligand recognition. In addition, there are several lines of evidence suggesting that Wnts engage several signalling modulators and alternative receptors by means of fatty acids as a critical contact residue. In the present article, we review our current understanding of Wnt acylation and its functional role in Wnt signalling regulation.
39
Vardjan, N., M. Stenovec, J. Jorgačevski, M. Kreft, and R. Zorec. "Fusion Pore: An Evolutionary Invention of Nucleated Cells." European Review 18, no. 3 (2010): 347–64. http://dx.doi.org/10.1017/s1062798710000074.
Full textAbstract:
This article outlines the lecture presented by Robert Zorec at the Academia Europea meeting in Liverpool on 19 September 2008, four decades after the Sherrington Lecture of Bernard Katz who, together with his colleagues, developed a number of paradigms addressing vesicles in chemical synapses. Vesicles are subcellular organelles that evolved in eukaryotic cells 1000 to 2000 million years ago. They store signalling molecules such as chemical messengers, which are essential for the function of neurons and endocrine cells in supporting the communication between tissues and organs in the human body. Upon a stimulus, the vesicle-stored signalling molecules (neurotransmitters or hormones) are released from cells. This event involves exocytosis, a fundamental biological process, consisting of the merger of the vesicle membrane with the plasma membrane. The two fusing membranes lead to the formation of an aqueous channel – the fusion pore – through which signalling molecules exit into the extracellular space or blood stream. The work of Bernard Katz and colleagues considered that vesicle cargo discharge initially requires the delivery of vesicles to the plasma membrane, where vesicles dock and get primed for fusion with the plasma membrane, and that stimulation initiates the formation of the transient fusion pore through which cargo molecules leave the vesicle lumen in an all-or-none-fashion. However, recent studies indicate that this may not be so simple. Here we highlight the novel findings which indicate that fusion pores are subject to regulations, which affect the release competence of a single vesicle. At least in pituitary lactotrophs, which are the subject of research in our laboratories, single vesicle release of peptide signalling molecules involves modulation of fusion pore diameter and fusion pore kinetics.
40
Chernogorova, Petya, and Robert Zeiser. "Ectonucleotidases in Solid Organ and Allogeneic Hematopoietic Cell Transplantation." Journal of Biomedicine and Biotechnology 2012 (2012): 1–17. http://dx.doi.org/10.1155/2012/208204.
Full textAbstract:
Extracellular nucleotides are ubiquitous signalling molecules which modulate distinct physiological and pathological processes. Nucleotide concentrations in the extracellular space are strictly regulated by cell surface enzymes, called ectonucleotidases, which hydrolyze nucleotides to the respective nucleosides. Recent studies suggest that ectonucleotidases play a significant role in inflammation by adjusting the balance between ATP, a widely distributed proinflammatory danger signal, and the anti-inflammatory mediator adenosine. There is increasing evidence for a central role of adenosine in alloantigen-mediated diseases such as solid organ graft rejection and acute graft-versus-host disease (GvHD). Solid organ and hematopoietic cell transplantation are established treatment modalities for a broad spectrum of benign and malignant diseases. Immunological complications based on the recognition of nonself-antigens between donor and recipient like transplant rejection and GvHD are still major challenges which limit the long-term success of transplantation. Studies in the past two decades indicate that purinergic signalling influences the severity of alloimmune responses. This paper focuses on the impact of ectonucleotidases, in particular, NTPDase1/CD39 and ecto-5′-nucleotidase/CD73, on allograft rejection, acute GvHD, and graft-versus-leukemia effect, and on possible clinical implications for the modulation of purinergic signalling after transplantation.
41
Herron, Lissa R., Maria Hill, Fleur Davey, and Frank J. Gunn-Moore. "The intracellular interactions of the L1 family of cell adhesion molecules." Biochemical Journal 419, no. 3 (2009): 519–31. http://dx.doi.org/10.1042/bj20082284.
Full textAbstract:
The L1 family of CAMs (cell adhesion molecules) has long aroused the interest of researchers, but primarily the extracellular interactions of these proteins have been elucidated. More recently, attention has turned to the intracellular signalling potentiated by transmembrane proteins and the cytoplasmic proteins with which they can interact. The present review brings up to date the current body of published knowledge for the intracellular interactions of L1-CAM family proteins and the potential importance of these interactions for the mechanisms of L1-CAM action.
42
Hayes, Anthony, Kazuyuki Sugahara, Brooke Farrugia, John M. Whitelock, Bruce Caterson, and James Melrose. "Biodiversity of CS–proteoglycan sulphation motifs: chemical messenger recognition modules with roles in information transfer, control of cellular behaviour and tissue morphogenesis." Biochemical Journal 475, no. 3 (2018): 587–620. http://dx.doi.org/10.1042/bcj20170820.
Full textAbstract:
Chondroitin sulphate (CS) glycosaminoglycan chains on cell and extracellular matrix proteoglycans (PGs) can no longer be regarded as merely hydrodynamic space fillers. Overwhelming evidence over recent years indicates that sulphation motif sequences within the CS chain structure are a source of significant biological information to cells and their surrounding environment. CS sulphation motifs have been shown to interact with a wide variety of bioactive molecules, e.g. cytokines, growth factors, chemokines, morphogenetic proteins, enzymes and enzyme inhibitors, as well as structural components within the extracellular milieu. They are therefore capable of modulating a panoply of signalling pathways, thus controlling diverse cellular behaviours including proliferation, differentiation, migration and matrix synthesis. Consequently, through these motifs, CS PGs play significant roles in the maintenance of tissue homeostasis, morphogenesis, development, growth and disease. Here, we review (i) the biodiversity of CS PGs and their sulphation motif sequences and (ii) the current understanding of the signalling roles they play in regulating cellular behaviour during tissue development, growth, disease and repair.
43
Nayeem, Sarmah B., Frank Arfuso, Arun Dharmarajan, and Jeffrey A. Keelan. "Role of Wnt signalling in early pregnancy." Reproduction, Fertility and Development 28, no. 5 (2016): 525. http://dx.doi.org/10.1071/rd14079.
Full textAbstract:
The integration of a complex network of signalling molecules promotes implantation of the blastocyst and development of the placenta. These processes are crucial for a successful pregnancy and fetal growth and development. The signalling network involves both cell–cell and cell–extracellular matrix communication. The family of secreted glycoprotein ligands, the Wnts, plays a major role in regulating a wide range of biological processes, including embryonic development, cell fate, proliferation, migration, stem cell maintenance, tumour suppression, oncogenesis and tissue homeostasis. Recent studies have provided evidence that Wnt signalling pathways play an important role in reproductive tissues and in early pregnancy events. The focus of this review is to summarise our present knowledge of expression, regulation and function of the Wnt signalling pathways in early pregnancy events of human and other model systems, and its association with pathological conditions. Despite our recent progress, much remains to be learned about Wnt signalling in human reproduction. The advancement of knowledge in this area has applications in the reduction of infertility and the incidence and morbidity of gestational diseases.
44
Muzio, M., N. Polentarutti, D. Bosisio, P. P. Manoj Kumar, and A. Mantovani. "Toll-like receptor family and signalling pathway." Biochemical Society Transactions 28, no. 5 (2000): 563–66. http://dx.doi.org/10.1042/bst0280563.
Full textAbstract:
Toll is a Drosophila gene essential for ontogenesis and anti-microbial resistance. Several orthologues of Toll have been identified and cloned in vertebrates, namely Toll-like receptors (TLRs). Human TLRs are a growing family of molecules involved in innate immunity. TLRs are characterized structurally by a cytoplasmic Toll/inter-leukin-1 receptor (TIR) domain and by extracellular leucine-rich repeats. TLRs characterized so far activate the MyD88/interleukin-l receptor-associated kinase (IRAK) signalling pathway. Genetic, gene-transfer and dominant-negative approaches have involved TLR family members (TLR2 and TLR4) in Gram-positive and Gram-negative bacteria recognition and signalling. Accumulating evidence suggests that TLR2 is also involved in signalling-receptor complexes that recognize components of yeast and mycobacteria. However, the definitive roles of other TLRs are still lacking. A systematic approach has been used to determine whether different human leucocyte populations selectively or specifically express TLR mRNA. Based on expression pattern, TLR can be classified as ubiquitous (TLR1), restricted (TLR2, TLR4 and TLR5) and specific (TLR3). Expression and regulation of distinct but overlapping ligand-recognition patterns may underlie the existence of a large, seemingly redundant TLR family. Alternatively, the expression of a TLR in a single cell type may indicate a specific role for this molecule in a restricted setting.
45
Gilbert, Sophie Jane, Cleo Selina Bonnet, and Emma Jane Blain. "Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage." International Journal of Molecular Sciences 22, no. 24 (2021): 13595. http://dx.doi.org/10.3390/ijms222413595.
Full textAbstract:
The composition and organisation of the extracellular matrix (ECM), particularly the pericellular matrix (PCM), in articular cartilage is critical to its biomechanical functionality; the presence of proteoglycans such as aggrecan, entrapped within a type II collagen fibrillar network, confers mechanical resilience underweight-bearing. Furthermore, components of the PCM including type VI collagen, perlecan, small leucine-rich proteoglycans—decorin and biglycan—and fibronectin facilitate the transduction of both biomechanical and biochemical signals to the residing chondrocytes, thereby regulating the process of mechanotransduction in cartilage. In this review, we summarise the literature reporting on the bidirectional reciprocity of the ECM in chondrocyte mechano-signalling and articular cartilage homeostasis. Specifically, we discuss studies that have characterised the response of articular cartilage to mechanical perturbations in the local tissue environment and how the magnitude or type of loading applied elicits cellular behaviours to effect change. In vivo, including transgenic approaches, and in vitro studies have illustrated how physiological loading maintains a homeostatic balance of anabolic and catabolic activities, involving the direct engagement of many PCM molecules in orchestrating this slow but consistent turnover of the cartilage matrix. Furthermore, we document studies characterising how abnormal, non-physiological loading including excessive loading or joint trauma negatively impacts matrix molecule biosynthesis and/or organisation, affecting PCM mechanical properties and reducing the tissue’s ability to withstand load. We present compelling evidence showing that reciprocal engagement of the cells with this altered ECM environment can thus impact tissue homeostasis and, if sustained, can result in cartilage degradation and onset of osteoarthritis pathology. Enhanced dysregulation of PCM/ECM turnover is partially driven by mechanically mediated proteolytic degradation of cartilage ECM components. This generates bioactive breakdown fragments such as fibronectin, biglycan and lumican fragments, which can subsequently activate or inhibit additional signalling pathways including those involved in inflammation. Finally, we discuss how bidirectionality within the ECM is critically important in enabling the chondrocytes to synthesise and release PCM/ECM molecules, growth factors, pro-inflammatory cytokines and proteolytic enzymes, under a specified load, to influence PCM/ECM composition and mechanical properties in cartilage health and disease.
46
Sygitowicz, Grażyna, Agata Maciejak-Jastrzębska, and Dariusz Sitkiewicz. "A Review of the Molecular Mechanisms Underlying Cardiac Fibrosis and Atrial Fibrillation." Journal of Clinical Medicine 10, no. 19 (2021): 4430. http://dx.doi.org/10.3390/jcm10194430.
Full textAbstract:
The cellular and molecular mechanism involved in the pathogenesis of atrial fibrosis are highly complex. We have reviewed the literature that covers the effectors, signal transduction and physiopathogenesis concerning extracellular matrix (ECM) dysregulation and atrial fibrosis in atrial fibrillation (AF). At the molecular level: angiotensin II, transforming growth factor-β1, inflammation, and oxidative stress are particularly important for ECM dysregulation and atrial fibrotic remodelling in AF. We conclude that the Ang-II-MAPK and TGF-β1-Smad signalling pathways play a major, central role in regulating atrial fibrotic remodelling in AF. The above signalling pathways induce the expression of genes encoding profibrotic molecules (MMP, CTGF, TGF-β1). An important mechanism is also the generation of reactive oxygen species. This pathway induced by the interaction of Ang II with the AT2R receptor and the activation of NADPH oxidase. Additionally, the interplay between cardiac MMPs and their endogenous tissue inhibitors of MMPs, is thought to be critical in atrial ECM metabolism and fibrosis. We also review recent evidence about the role of changes in the miRNAs expression in AF pathophysiology and their potential as therapeutic targets. Furthermore, keeping the balance between miRNA molecules exerting anti-/profibrotic effects is of key importance for the control of atrial fibrosis in AF.
47
Prevarskaya, Natalia, Halima Ouadid-Ahidouch, Roman Skryma, and Yaroslav Shuba. "Remodelling of Ca 2+ transport in cancer: how it contributes to cancer hallmarks?" Philosophical Transactions of the Royal Society B: Biological Sciences 369, no. 1638 (2014): 20130097. http://dx.doi.org/10.1098/rstb.2013.0097.
Full textAbstract:
Cancer involves defects in the mechanisms underlying cell proliferation, death and migration. Calcium ions are central to these phenomena, serving as major signalling agents with spatial localization, magnitude and temporal characteristics of calcium signals ultimately determining cell's fate. Cellular Ca 2+ signalling is determined by the concerted action of a molecular Ca 2+ -handling toolkit which includes: active energy-dependent Ca 2+ transporters, Ca 2+ -permeable ion channels, Ca 2+ -binding and storage proteins, Ca 2+ -dependent effectors. In cancer, because of mutations, aberrant expression, regulation and/or subcellular targeting of Ca 2+ -handling/transport protein(s) normal relationships among extracellular, cytosolic, endoplasmic reticulum and mitochondrial Ca 2+ concentrations or spatio-temporal patterns of Ca 2+ signalling become distorted. This causes deregulation of Ca 2+ -dependent effectors that control signalling pathways determining cell's behaviour in a way to promote pathophysiological cancer hallmarks such as enhanced proliferation, survival and invasion. Despite the progress in our understanding of Ca 2+ homeostasis remodelling in cancer cells as well as in identification of the key Ca 2+ -transport molecules promoting certain malignant phenotypes, there is still a lot of work to be done to transform fundamental findings and concepts into new Ca 2+ transport-targeting tools for cancer diagnosis and treatment.
48
Adams, Josephine Clare. "Molecular organisation of cell–matrix contacts: essential multiprotein assemblies in cell and tissue function." Expert Reviews in Molecular Medicine 4, no. 1 (2002): 1–24. http://dx.doi.org/10.1017/s1462399402004039.
Full textAbstract:
The adhesion of cells to their surrounding extracellular matrix has vital roles in embryonic development, inflammatory responses, wound healing and adult tissue homeostasis. Cells attach to extracellular matrix by specific cell-surface receptors, of which the integrins and transmembrane proteoglycans are major representatives. The engagement of adhesion receptors triggers assembly of functional matrix contacts, in which bound matrix components, adhesion receptors and associated intracellular cytoskeletal and signalling molecules form large, localised multiprotein complexes. This review discusses the functional categories of matrix contacts, examples of the biological roles of matrix contacts in normal physiology, and examples of the ways in which abnormalities of matrix contacts are associated with major human diseases.
49
Menéndez Méndez, Aida, Jonathon Smith, and Tobias Engel. "Neonatal Seizures and Purinergic Signalling." International Journal of Molecular Sciences 21, no. 21 (2020): 7832. http://dx.doi.org/10.3390/ijms21217832.
Full textAbstract:
Neonatal seizures are one of the most common comorbidities of neonatal encephalopathy, with seizures aggravating acute injury and clinical outcomes. Current treatment can control early life seizures; however, a high level of pharmacoresistance remains among infants, with increasing evidence suggesting current anti-seizure medication potentiating brain damage. This emphasises the need to develop safer therapeutic strategies with a different mechanism of action. The purinergic system, characterised by the use of adenosine triphosphate and its metabolites as signalling molecules, consists of the membrane-bound P1 and P2 purinoreceptors and proteins to modulate extracellular purine nucleotides and nucleoside levels. Targeting this system is proving successful at treating many disorders and diseases of the central nervous system, including epilepsy. Mounting evidence demonstrates that drugs targeting the purinergic system provide both convulsive and anticonvulsive effects. With components of the purinergic signalling system being widely expressed during brain development, emerging evidence suggests that purinergic signalling contributes to neonatal seizures. In this review, we first provide an overview on neonatal seizure pathology and purinergic signalling during brain development. We then describe in detail recent evidence demonstrating a role for purinergic signalling during neonatal seizures and discuss possible purine-based avenues for seizure suppression in neonates.
50
REES, D. Aled, Maurice F. SCANLON, and Jack HAM. "Novel insights into how purines regulate pituitary cell function." Clinical Science 104, no. 5 (2003): 467–81. http://dx.doi.org/10.1042/cs20030053.
Full textAbstract:
Purine nucleosides and nucleotides are widely distributed substances that exhibit a diverse range of effects in a number of tissues, acting as important extracellular signalling molecules in addition to their more established roles in cellular metabolism. They mediate their effects via activation of distinct cell surface receptors, termed adenosine (or P1) and P2 purinergic receptors. Although roles for adenosine and adenine nucleotides have been described previously in the pituitary gland, the distribution of the receptor subtypes and the effects of their activation on pituitary function are not well defined. Recent evidence, however, has emerged to describe a complex signalling system for purines in the pituitary gland. Data from a variety of studies have shown that the expression pattern, number and affinity of adenosine and/or P2 receptors may be cell-type specific and that non-endocrine in addition to endocrine cells elaborate these receptors. These variations, along with the diverse range of signalling pathways activated, dictate the response of individual cell types to extracellular purines, with roles now emerging for these substances in the regulation of hormone release, pituitary cell proliferation and cytokine/growth factor expression. In this review, we discuss these advances and examine some implications for pituitary growth control and the response of the hypothalamic–pituitary–adrenal axis to stress and inflammation.