To see the other types of publications on this topic, follow the link: Syndecans.
Journal articles on the topic 'Syndecans'
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 'Syndecans.'
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
CAREY, David J. "Syndecans: multifunctional cell-surface co-receptors." Biochemical Journal 327, no. 1 (October 1, 1997): 1–16. http://dx.doi.org/10.1042/bj3270001.
Full textAbstract:
This review will summarize our current state of knowledge of the structure, biochemical properties and functions of syndecans, a family of transmembrane heparan sulphate proteoglycans. Syndecans bind a variety of extracellular ligands via their covalently attached heparan sulphate chains. Syndecans have been proposed to play a role in a variety of cellular functions, including cell proliferation and cell–matrix and cell–cell adhesion. Syndecan expression is highly regulated and is cell-type- and developmental-stage-specific. The main function of syndecans appears to be to modulate the ligand-dependent activation of primary signalling receptors at the cell surface. Principal functions of the syndecan core proteins are to target the heparan sulphate chains to the appropriate plasma-membrane compartment and to interact with components of the actin-based cytoskeleton. Several functions of the syndecans, including syndecan oligomerization and actin cytoskeleton association, have been localized to specific structural domains of syndecan core proteins.
2
Kim, C. W., O. A. Goldberger, R. L. Gallo, and M. Bernfield. "Members of the syndecan family of heparan sulfate proteoglycans are expressed in distinct cell-, tissue-, and development-specific patterns." Molecular Biology of the Cell 5, no. 7 (July 1994): 797–805. http://dx.doi.org/10.1091/mbc.5.7.797.
Full textAbstract:
The syndecans are a gene family of four transmembrane heparan sulfate proteoglycans that bind, via their HS chains, diverse components of the cellular microenvironment. To evaluate the expression of the individual syndecans, we prepared cDNA probes to compare mRNA levels in various adult mouse tissues and cultured mouse cells representing various epithelial, fibroblastic, endothelial, and neural cell types and B cells at various stages of differentiation. We also prepared antibody probes to assess whether the extracellular domains of the individual syndecans are shed into the conditioned media of cultured cells. Our results show that all cells and tissues studied, except B-stem cells, express at least one syndecan family member; most cells and tissues express multiple syndecans. However, each syndecan family member is expressed selectively in cell-, tissue-, and development-specific patterns. The extracellular domain of all syndecan family members is shed as an intact proteoglycan. Thus, most, if not all, cells acquire a distinctive repertoire of the four syndecan family members as they differentiate, resulting in selective patterns of expression that likely reflect distinct functions.
3
Mitsou, Ioli, Hinke A. B. Multhaupt, and John R. Couchman. "Proteoglycans, ion channels and cell–matrix adhesion." Biochemical Journal 474, no. 12 (May 25, 2017): 1965–79. http://dx.doi.org/10.1042/bcj20160747.
Full textAbstract:
Cell surface proteoglycans comprise a transmembrane or membrane-associated core protein to which one or more glycosaminoglycan chains are covalently attached. They are ubiquitous receptors on nearly all animal cell surfaces. In mammals, the cell surface proteoglycans include the six glypicans, CD44, NG2 (CSPG4), neuropilin-1 and four syndecans. A single syndecan is present in invertebrates such as nematodes and insects. Uniquely, syndecans are receptors for many classes of proteins that can bind to the heparan sulphate chains present on syndecan core proteins. These range from cytokines, chemokines, growth factors and morphogens to enzymes and extracellular matrix (ECM) glycoproteins and collagens. Extracellular interactions with other receptors, such as some integrins, are mediated by the core protein. This places syndecans at the nexus of many cellular responses to extracellular cues in development, maintenance, repair and disease. The cytoplasmic domains of syndecans, while having no intrinsic kinase activity, can nevertheless signal through binding proteins. All syndecans appear to be connected to the actin cytoskeleton and can therefore contribute to cell adhesion, notably to the ECM and migration. Recent data now suggest that syndecans can regulate stretch-activated ion channels. The structure and function of the syndecans and the ion channels are reviewed here, along with an analysis of ion channel functions in cell–matrix adhesion. This area sheds new light on the syndecans, not least since evidence suggests that this is an evolutionarily conserved relationship that is also potentially important in the progression of some common diseases where syndecans are implicated.
4
Betriu, Nausika, Juan Bertran-Mas, Anna Andreeva, and Carlos E. Semino. "Syndecans and Pancreatic Ductal Adenocarcinoma." Biomolecules 11, no. 3 (February 25, 2021): 349. http://dx.doi.org/10.3390/biom11030349.
Full textAbstract:
Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.
5
Hudák, Anett, Annamária Letoha, László Szilák, and Tamás Letoha. "Contribution of Syndecans to the Cellular Entry of SARS-CoV-2." International Journal of Molecular Sciences 22, no. 10 (May 19, 2021): 5336. http://dx.doi.org/10.3390/ijms22105336.
Full textAbstract:
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel emerging pathogen causing an unprecedented pandemic in 21st century medicine. Due to the significant health and economic burden of the current SARS-CoV-2 outbreak, there is a huge unmet medical need for novel interventions effectively blocking SARS-CoV-2 infection. Unknown details of SARS-CoV-2 cellular biology hamper the development of potent and highly specific SARS-CoV-2 therapeutics. Angiotensin-converting enzyme-2 (ACE2) has been reported to be the primary receptor for SARS-CoV-2 cellular entry. However, emerging scientific evidence suggests the involvement of additional membrane proteins, such as heparan sulfate proteoglycans, in SARS-CoV-2 internalization. Here, we report that syndecans, the evolutionarily conserved family of transmembrane proteoglycans, facilitate the cellular entry of SARS-CoV-2. Among syndecans, the lung abundant syndecan-4 was the most efficient in mediating SARS-CoV-2 uptake. The S1 subunit of the SARS-CoV-2 spike protein plays a dominant role in the virus’s interactions with syndecans. Besides the polyanionic heparan sulfate chains, other parts of the syndecan ectodomain, such as the cell-binding domain, also contribute to the interaction with SARS-CoV-2. During virus internalization, syndecans colocalize with ACE2, suggesting a jointly shared internalization pathway. Both ACE2 and syndecan inhibitors exhibited significant efficacy in reducing the cellular entry of SARS-CoV-2, thus supporting the complex nature of internalization. Data obtained on syndecan specific in vitro assays present syndecans as novel cellular targets of SARS-CoV-2 and offer molecularly precise yet simple strategies to overcome the complex nature of SARS-CoV-2 infection.
6
De Rossi, Giulia, and James R. Whiteford. "Syndecans in angiogenesis and endothelial cell biology." Biochemical Society Transactions 42, no. 6 (November 17, 2014): 1643–46. http://dx.doi.org/10.1042/bst20140232.
Full textAbstract:
Syndecans are multifunctional heparan sulfate proteoglycans (HSPGs) with roles in cell adhesion, migration, receptor trafficking and growth-factor interactions and signalling. Studies using syndecan null animals have revealed limited roles for syndecans during development; however, under conditions of challenge or insult, several phenotypes have emerged. Angiogenesis is an important process both in development and in wound healing, but also in pathologies such as cancer and chronic inflammatory conditions. In the present paper, we summarize the main studies elucidating the role of syndecans in angiogenesis and their potential as novel therapeutic targets.
7
Hudák, Anett, Katalin Jósvay, Ildikó Domonkos, Annamária Letoha, László Szilák, and Tamás Letoha. "The Interplay of Apoes with Syndecans in Influencing Key Cellular Events of Amyloid Pathology." International Journal of Molecular Sciences 22, no. 13 (June 30, 2021): 7070. http://dx.doi.org/10.3390/ijms22137070.
Full textAbstract:
Apolipoprotein E (ApoE) isoforms exert intricate effects on cellular physiology beyond lipid transport and metabolism. ApoEs influence the onset of Alzheimer’s disease (AD) in an isoform-dependent manner: ApoE4 increases AD risk, while ApoE2 decreases it. Previously we demonstrated that syndecans, a transmembrane proteoglycan family with increased expression in AD, trigger the aggregation and modulate the cellular uptake of amyloid beta (Aβ). Utilizing our previously established syndecan-overexpressing cellular assays, we now explore how the interplay of ApoEs with syndecans contributes to key events, namely uptake and aggregation, in Aβ pathology. The interaction of ApoEs with syndecans indicates isoform-specific characteristics arising beyond the frequently studied ApoE–heparan sulfate interactions. Syndecans, and among them the neuronal syndecan-3, increased the cellular uptake of ApoEs, especially ApoE2 and ApoE3, while ApoEs exerted opposing effects on syndecan-3-mediated Aβ uptake and aggregation. ApoE2 increased the cellular internalization of monomeric Aβ, hence preventing its extracellular aggregation, while ApoE4 decreased it, thus helping the buildup of extracellular plaques. The contrary effects of ApoE2 and ApoE4 remained once Aβ aggregated: while ApoE2 reduced the uptake of Aβ aggregates, ApoE4 facilitated it. Fibrillation studies also revealed ApoE4′s tendency to form fibrillar aggregates. Our results uncover yet unknown details of ApoE cellular biology and deepen our molecular understanding of the ApoE-dependent mechanism of Aβ pathology.
8
Finsen, Alexandra Vanessa, Per Reidar Woldbaek, Jian Li, Jiaping Wu, Torstein Lyberg, Theis Tønnessen, and Geir Christensen. "Increased syndecan expression following myocardial infarction indicates a role in cardiac remodeling." Physiological Genomics 16, no. 3 (February 13, 2004): 301–8. http://dx.doi.org/10.1152/physiolgenomics.00144.2002.
Full textAbstract:
Finsen, Alexandra Vanessa, Per Reidar Woldbaek, Jian Li, Jiaping Wu, Torstein Lyberg, Theis Tonnessen, and Geir Christensen. Increased syndecan expression following myocardial infarction indicates a role in cardiac remodeling. Physiol Genomics 16: 301-308, 2004. First published November 18, 2003; 10.1152/physi-olgenomics. 00144.2002.—The purpose of this study was to identify essential genes involved in myocardial growth and remodeling following myocardial infarction (MI). Left ventricular noninfarcted tissues from six mice subjected to MI under general anesthesia and from six sham-operated mice were obtained 1 wk after primary surgery and analyzed by means of cDNA filter arrays. Out of a total of 1,176 genes, 641 were consistently expressed, twenty-three were upregulated and thirteen downregulated. Five genes were only expressed following MI. Syndecan-3, a transmembranous heparan sulfate proteoglycan, was found to be upregulated together with a transcriptional activator of syndecans, Wilms tumor protein 1 (WT-1). Northern blotting demonstrated a significant upregulation of syndecan-1, -2, -3, and -4, WT-1, fibronectin, and basic fibroblast growth factor (FGF) receptor 1. Furthermore, Western blot analysis showed statistically significant increases in protein levels for syndecan-3 and -4. In conclusion, we have identified a subset of genes with increased expression in noninfarcted left ventricular tissue following MI, including syndecans 1–4, WT-1, fibronectin, collagen 6A, and FGF receptor 1. Since the syndecans link the cytoskeleton to the extracellular matrix and function as required coreceptors for FGF, we suggest a role for the syndecans in cardiac remodeling following MI.
9
Termini, Christina, Michelle Li, Joyce Kim, Liman Zhao, and John P. Chute. "Syndecan-2 Surface Expression Identifies Hematopoietic Stem Cells with Increased Repopulating Capacity." Blood 132, Supplement 1 (November 29, 2018): 1273. http://dx.doi.org/10.1182/blood-2018-99-110701.
Full textAbstract:
Abstract Syndecans are transmembrane glycoproteins, which can regulate cell proliferation, growth, and adhesion through interactions with neighboring proteins within the plasma membrane or at the cytoplasmic interface. Although syndecans have been described to regulate aberrant signaling in hematological malignances, the role of syndecans in regulating normal hematopoietic stem cell (HSC) proliferation, differentiation, and self-renewal is largely unknown. We demonstrate that syndecan-1 and syndecan-3 are expressed on the surface of < 10% of murine hematopoietic stem and progenitor cells, whereas, syndecan-4 is expressed on 50% of lineage negative (Lin-) progenitor cells and 98% of c-Kit+Sca-1+Lin- (KSL) hematopoietic stem/progenitor cells, KSL CD34-CD48-CD150+/- short-term HSCs, and 100% of CD34-CD48-CD150+ long-term HSCs. Interestingly, we find that syndecan-2 is expressed by 11% of KSL CD34-CD48-CD150+/- short-term HSCs and 36% of CD34-CD48-CD150+ long-term HSCs. More specifically, our data demonstrate a 15-fold increase in syndecan-2 surface expression on KSL CD34-CD48-CD150+ HSCs compared to Lin- progenitor cells (p<.0001, ****). Collectively, these data suggest that syndecan-2 may be a marker for long-term HSCs. In keeping with this hypothesis, we found that syndecan-2+ CD34- KSL cells produce two-fold more granulocyte, erythrocyte, monocyte, megakaryocyte (GEMM) colonies compared to syndecan-2- CD34- KSL cells (p=.0017, **). Cell cycle analyses revealed a significant increase in BrdU incorporation in syndecan-2+ KSL cells compared to syndecan-2- KSL cells (90% versus 40%, p<.0001, ****). Competitive repopulation assays comparing syndecan-2+ or syndecan-2- CD34- KSL bone marrow cells demonstrated that mice transplanted with syndecan-2+ CD34- KSL cells displayed threefold increased donor multilineage hematopoietic cell repopulation compared to mice transplanted with syndecan-2- CD34- KSL cells. These data suggest that syndecan-2 expression marks a highly proliferative population of HSCs with increased multilineage repopulating capacity and that syndecan-2+ HSCs can be readily isolated to enhance the efficacy of hematopoietic cell transplantation. Disclosures No relevant conflicts of interest to declare.
10
Gopal, Sandeep, Pernille Søgaard, Hinke A. B. Multhaupt, Csilla Pataki, Elena Okina, Xiaojie Xian, Mikael E. Pedersen, et al. "Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels." Journal of Cell Biology 210, no. 7 (September 21, 2015): 1199–211. http://dx.doi.org/10.1083/jcb.201501060.
Full textAbstract:
Transmembrane heparan sulfate proteoglycans regulate multiple aspects of cell behavior, but the molecular basis of their signaling is unresolved. The major family of transmembrane proteoglycans is the syndecans, present in virtually all nucleated cells, but with mostly unknown functions. Here, we show that syndecans regulate transient receptor potential canonical (TRPCs) channels to control cytosolic calcium equilibria and consequent cell behavior. In fibroblasts, ligand interactions with heparan sulfate of syndecan-4 recruit cytoplasmic protein kinase C to target serine714 of TRPC7 with subsequent control of the cytoskeleton and the myofibroblast phenotype. In epidermal keratinocytes a syndecan–TRPC4 complex controls adhesion, adherens junction composition, and early differentiation in vivo and in vitro. In Caenorhabditis elegans, the TRPC orthologues TRP-1 and -2 genetically complement the loss of syndecan by suppressing neuronal guidance and locomotory defects related to increases in neuronal calcium levels. The widespread and conserved syndecan–TRPC axis therefore fine tunes cytoskeletal organization and cell behavior.
11
Bernfield, Merton, Michael T. Hinkes, and Richard L. Gallo. "Developmental expression of the syndecans: possible function and regulation." Development 119, Supplement (December 1, 1993): 205–12. http://dx.doi.org/10.1242/dev.119.supplement.205.
Full textAbstract:
Recent work has made clear that heparan sulfate at the cell surface is essential for a wide variety of interactions of cells with their microenvironment , including the action of growth factors, extracellular matrix, proteases and protease inhibitors. A major source of this cell surface heparan sulfate is a multigene family of proteoglycans, the syndecans that are expressed developmentally in association with changes in tissue organization and morphology and induced during wound repair. In this review, we describe mechanisms underlyin g the differential expression of the syndecans, focusing on syndecan-1. The induction of syndecan-1 can result from soluble extracellular factor(s) acting at multiple levels of cellular regulation. At the transcriptional level, the promoter of the murine syndecan-1 gene contains potential recognition sites for several well-known regulatory genes, including Hox and MyoD family members. Because changes in syndecan expression enable cells to become more or less responsive to their microenvironment, understanding these regulatory mechanisms can lead to an improved understanding of how cellular behavior is controlled during development and wound repair.
12
Araki, Eri, Yutaka Momota, Takeshi Togo, Miki Tanioka, Kentaro Hozumi, Motoyoshi Nomizu, Yoshiki Miyachi, and Atsushi Utani. "Clustering of Syndecan-4 and Integrin β1 by Laminin α3 Chain–derived Peptide Promotes Keratinocyte Migration." Molecular Biology of the Cell 20, no. 13 (July 2009): 3012–24. http://dx.doi.org/10.1091/mbc.e08-09-0977.
Full textAbstract:
Syndecans function as receptors for extracellular matrix (ECM) with integrins in cell spreading. However, the molecular mechanism of their specific involvement in cell migration or in wound healing has not been elucidated yet. Here, we report that a synthetic peptide, PEP75, which contains the syndecan-binding sequence of the laminin α3LG4 module, induces keratinocyte migration in in vitro and in vivo. Soluble PEP75 induced the clustering of syndecan-4 and conformation-modified integrin β1 colocalized with syndecan-4 in soluble PEP75-induced clusters. Treatment of cells in solution with PEP75 resulted in the exposure of the P4G11 antibody epitope of integrin β1 in immunostaining as well as in flow cytometry and augmented integrin β1–dependent cell adhesion to ECM. Pulldown assays demonstrated that PEP75 bound to syndecan-4, but not to integrin β1. A siRNA study revealed a role for syndecan-4 in PEP75-induced up-regulation of P4G11 antibody binding and migration of HaCaT cells. We conclude that binding of soluble PEP75 to syndecan-4 induces the coupling of integrin β1, which is associated with integrin β1-conformational changes and activation, and leads to keratinocyte migration. To activate integrin function through syndecans could be a novel therapeutic approach for chronic wound.
13
Tkachenko, Eugene, John M. Rhodes, and Michael Simons. "Syndecans." Circulation Research 96, no. 5 (March 18, 2005): 488–500. http://dx.doi.org/10.1161/01.res.0000159708.71142.c8.
Full text
14
Iba, Kousuke, Reidar Albrechtsen, Brent Gilpin, Camilla Fröhlich, Frosty Loechel, Anna Zolkiewska, Kazuhiro Ishiguro, et al. "The Cysteine-Rich Domain of Human Adam 12 Supports Cell Adhesion through Syndecans and Triggers Signaling Events That Lead to β1 Integrin–Dependent Cell Spreading." Journal of Cell Biology 149, no. 5 (May 29, 2000): 1143–56. http://dx.doi.org/10.1083/jcb.149.5.1143.
Full textAbstract:
The ADAMs (a disintegrin and metalloprotease) family of proteins is involved in a variety of cellular interactions, including cell adhesion and ecto- domain shedding. Here we show that ADAM 12 binds to cell surface syndecans. Three forms of recombinant ADAM 12 were used in these experiments: the cys-teine-rich domain made in Escherichia coli (rADAM 12-cys), the disintegrin-like and cysteine-rich domain made in insect cells (rADAM 12-DC), and full-length human ADAM 12-S tagged with green fluorescent protein made in mammalian cells (rADAM 12-GFP). Mesenchymal cells specifically and in a dose-dependent manner attach to ADAM 12 via members of the syndecan family. After binding to syndecans, mesenchymal cells spread and form focal adhesions and actin stress fibers. Integrin β1 was responsible for cell spreading because function-blocking monoclonal antibodies completely inhibited cell spreading, and chondroblasts lacking β1 integrin attached but did not spread. These data suggest that mesenchymal cells use syndecans as the initial receptor for the ADAM 12 cysteine-rich domain–mediated cell adhesion, and then the β1 integrin to induce cell spreading. Interestingly, carcinoma cells attached but did not spread on ADAM 12. However, spreading could be efficiently induced by the addition of either 1 mM Mn2+ or the β1 integrin–activating monoclonal antibody 12G10, suggesting that in these carcinoma cells, the ADAM 12–syndecan complex fails to modulate the function of β1 integrin.
15
Huang, Chun-Ping, Chao-Min Cheng, Hong-Lin Su, and Yi-Wen Lin. "Syndecan-4 Promotes Epithelial Tumor Cells Spreading and Regulates the Turnover of PKCα Activity under Mechanical Stimulation on the Elastomeric Substrates." Cellular Physiology and Biochemistry 36, no. 4 (2015): 1291–304. http://dx.doi.org/10.1159/000430297.
Full textAbstract:
Background: Heparan sulfate proteoglycans (HSPGs) at the cell surface play an important role in cell adhesion, spreading, formation of focal adhesion complexes (FACs), and sensing mechanical stress. Syndecans are members of the HSPGs family and are highly expressed in various tumor cells. Syndecan-4 (SDC4) is a unique member of syndecans that activates protein kinase C alpha (PKCα). However, syndecan-4 in tumor cells development is not clear when receiving mechanical stress. Aims: Here we investigate the role of syndecan-4 in tumor cells spreading and its downstream kinases under mechanical stimulation. Methods: Epithelial tumor cells were seeded onto elastomeric polydimethylsiloxane (PDMS) membranes coated with poly-L-lysine (Pl), fibronectin (Fn), or anti-SDC4 antibody and stretched with a modified pressure-driven cell-stretching (PreCS) device. Results: When cells received mechanical stimulation, engagement of syndecan-4 promoted the phosphorylation of focal adhesion kinase (FAK) at tyrosine 397 and PKCα at serine 657. Furthermore, we analyzed the cell contractility marker—myosin light chain 2 (MLC2) in 30 min time courses. The levels of phosphorylated MLC2 at serine19 were augmented through ligations of syndecan-4 but not integrin binding motif (RGD) at 10 min mechanical stimulation and were suppressed at 30 min and this phenomenon was associated with the activity of PKCα. Conclusion: Our data demonstrate that syndecan-4 is essential for transmitting the mechanotransduction signals via activation of PKCα and is important for tumor cells spreading, assembly of actin cytoskeleton and cell contractility.
16
Wang, Haiyao, Haining Jin, DeannaLee M. Beauvais, and Alan C. Rapraeger. "Cytoplasmic Domain Interactions of Syndecan-1 and Syndecan-4 with α6β4 Integrin Mediate Human Epidermal Growth Factor Receptor (HER1 and HER2)-dependent Motility and Survival." Journal of Biological Chemistry 289, no. 44 (September 8, 2014): 30318–32. http://dx.doi.org/10.1074/jbc.m114.586438.
Full textAbstract:
Epithelial cells are highly dependent during wound healing and tumorigenesis on the α6β4 integrin and its association with receptor tyrosine kinases. Previous work showed that phosphorylation of the β4 subunit upon matrix engagement depends on the matrix receptor syndecan (Sdc)-1 engaging the cytoplasmic domain of the β4 integrin and coupling of the integrin to human epidermal growth factor receptor-2 (HER2). In this study, HER2-dependent migration activated by matrix engagement is compared with migration stimulated by EGF. We find that whereas HER2-dependent migration depends on Sdc1, EGF-dependent migration depends on a complex consisting of human epidermal growth factor receptor-1 (HER1, commonly known as EGFR), α6β4, and Sdc4. The two syndecans recognize distinct sites at the extreme C terminus of the β4 integrin cytoplasmic domain. The binding motif in Sdc1 is QEEXYX, composed in part by its syndecan-specific variable (V) region and in part by the second conserved (C2) region that it shares with other syndecans. A cell-penetrating peptide containing this sequence competes for HER2-dependent epithelial migration and carcinoma survival, although it is without effect on the EGFR-stimulated mechanism. β4 mutants bearing mutations specific for Sdc1 and Sdc4 recognition act as dominant negative mutants to block cell spreading or cell migration that depends on HER2 or EGFR, respectively. The interaction of the α6β4 integrin with the syndecans appears critical for it to be utilized as a signaling platform; migration depends on α3β1 integrin binding to laminin 332 (LN332; also known as laminin 5), whereas antibodies that block α6β4 binding are without effect. These findings indicate that specific syndecan family members are likely to have key roles in α6β4 integrin activation by receptor tyrosine kinases.
17
Hillemeyer, Lara, Nancy Adriana Espinoza-Sanchez, Burkhard Greve, Nourhan Hassan, Anca Chelariu-Raicu, Ludwig Kiesel, and Martin Götte. "The Cell Surface Heparan Sulfate Proteoglycan Syndecan-3 Promotes Ovarian Cancer Pathogenesis." International Journal of Molecular Sciences 23, no. 10 (May 21, 2022): 5793. http://dx.doi.org/10.3390/ijms23105793.
Full textAbstract:
Syndecans are transmembrane heparan sulfate proteoglycans that integrate signaling at the cell surface. By interacting with cytokines, signaling receptors, proteases, and extracellular matrix proteins, syndecans regulate cell proliferation, metastasis, angiogenesis, and inflammation. We analyzed public gene expression datasets to evaluate the dysregulation and potential prognostic impact of Syndecan-3 in ovarian cancer. Moreover, we performed functional in vitro analysis in syndecan-3-siRNA-treated SKOV3 and CAOV3 ovarian cancer cells. In silico analysis of public gene array datasets revealed that syndecan-3 mRNA expression was significantly increased 5.8-fold in ovarian cancer tissues (n = 744) and 3.4-fold in metastases (n = 44) compared with control tissue (n = 46), as independently confirmed in an RNAseq dataset on ovarian serous cystadenocarcinoma tissue (n = 374, controls: n = 133, 3.5-fold increase tumor vs. normal). Syndecan-3 siRNA knockdown impaired 3D spheroid growth and colony formation as stemness-related readouts in SKOV3 and CAOV3 cells. In SKOV3, but not in CAOV3 cells, syndecan-3 depletion reduced cell viability both under basal conditions and under chemotherapy with cisplatin, or cisplatin and paclitaxel. While analysis of the SIOVDB database did not reveal differences in Syndecan-3 expression between patients, sensitive, resistant or refractory to chemotherapy, KM Plotter analysis of 1435 ovarian cancer patients revealed that high syndecan-3 expression was associated with reduced survival in patients treated with taxol and platin. At the molecular level, a reduction in Stat3 activation and changes in the expression of Wnt and notch signaling constituents were observed. Our study suggests that up-regulation of syndecan-3 promotes the pathogenesis of ovarian cancer by modulating stemness-associated pathways.
18
Whiteford, James R., and John R. Couchman. "A Conserved NXIP Motif Is Required for Cell Adhesion Properties of the Syndecan-4 Ectodomain." Journal of Biological Chemistry 281, no. 43 (August 25, 2006): 32156–63. http://dx.doi.org/10.1074/jbc.m605553200.
Full textAbstract:
Syndecans are cell surface proteoglycans involved in cell adhesion and motility. Syndecan-4 is an important component of focal adhesions and is involved in cytoskeletal reorganization. Previous work has shown that the syndecan-4 ectodomain can support cell attachment. Here, three vertebrate syndecan-4 ectodomains were compared, including that of the zebrafish, and we have demonstrated that the cell binding activity of the syndecan-4 ectodomain is conserved. Cell adhesion to the syndecan-4 ectodomain appears to be a characteristic of mesenchymal cells. Comparison of syndecan-4 ectodomain sequences led to the identification of three conserved regions of sequence, of which the NXIP motif is important for cell binding activity. We have shown that cell adhesion to the syndecan-4 ectodomain involves β1 integrins in several cell types.
19
MUNESUE, Seiichi, Yuri KUSANO, Kayoko OGURI, Naoki ITANO, Yasuo YOSHITOMI, Hayao NAKANISHI, Ikuo YAMASHINA, and Minoru OKAYAMA. "The role of syndecan-2 in regulation of actin-cytoskeletal organization of Lewis lung carcinoma-derived metastatic clones." Biochemical Journal 363, no. 2 (April 8, 2002): 201–9. http://dx.doi.org/10.1042/bj3630201.
Full textAbstract:
Syndecans, a family of transmembrane heparan sulphate proteoglycans, contribute to various biological processes, including adhesion, motility, proliferation, differentiation and morphogenesis. We document here the involvement of syndecan-2 acting alone or co-operatively with integrin α5β1, for regulation of actin-cytoskeletal organization on cell adhesion to fibronectin, using fibronectin-recombinant polypeptides containing the ligands for either or both of these receptors as substrata. Lewis lung carcinoma-derived low-metastatic P29 cells binding to the substrata by both receptors formed actin stress fibres, whereas those binding by syndecan-2 or integrin α5β1 alone formed filopodia or cortex actin. In contrast, higher metastatic LM66-H11 cells formed cortex actin even on substrata containing both ligands. Northern-blot and flow-cytometric analyses revealed that syndecan-2 expression in LM66-H11 cells was significantly lower (1/4.5 in mRNA and 1/8 in cell-surface expression) than in P29 cells, whereas expression levels of integrin α5β1 and other syndecans were similar in both cell types. These results suggest that the failure of LM66-H11 to form stress fibres is due to a lower expression of syndecan-2 than that due to a threshold for its function. This was confirmed by the finding that overexpression of syndecan-2 by transfection of its cDNA into LM66-H11 cells caused the formation of stress fibres on the fibronectin substratum. These in vitro cellular responses of the two clones might reflect their in vivo situation in primary tumours in which P29 cells with a stroma-inducing capacity were immediately surrounded by fibronectin-rich matrix formed by the induced stromal cells, whereas LM66-H11 cells without such capacity were not surrounded by a similar matrix.
20
Palomino, Rafael, Hsiau-Wei Lee, and Glenn L. Millhauser. "The agouti-related peptide binds heparan sulfate through segments critical for its orexigenic effects." Journal of Biological Chemistry 292, no. 18 (March 6, 2017): 7651–61. http://dx.doi.org/10.1074/jbc.m116.772822.
Full textAbstract:
Syndecans potently modulate agouti-related peptide (AgRP) signaling in the central melanocortin system. Through heparan sulfate moieties, syndecans are thought to anchor AgRP near its receptor, enhancing its orexigenic effects. Original work proposed that the N-terminal domain of AgRP facilitates this interaction. However, this is not compatible with evidence that this domain is posttranslationally cleaved. Addressing this long-standing incongruity, we used calorimetry and magnetic resonance to probe interactions of AgRP peptides with glycosaminoglycans, including heparan sulfate. We show that mature, cleaved, C-terminal AgRP, not the N-terminal domain, binds heparan sulfate. NMR shows that the binding site consists of regions distinct from the melanocortin receptor-binding site. Using a library of designed AgRP variants, we find that the strength of the syndecan interaction perfectly tracks orexigenic action. Our data provide compelling evidence that AgRP is a heparan sulfate-binding protein and localizes critical regions in the AgRP structure required for this interaction.
21
Kalia, Manjula, Vivek Chandra, Sheikh Abdul Rahman, Deepak Sehgal, and Shahid Jameel. "Heparan Sulfate Proteoglycans Are Required for Cellular Binding of the Hepatitis E Virus ORF2 Capsid Protein and for Viral Infection." Journal of Virology 83, no. 24 (October 7, 2009): 12714–24. http://dx.doi.org/10.1128/jvi.00717-09.
Full textAbstract:
ABSTRACT The hepatitis E virus (HEV), a nonenveloped RNA virus, is the causative agent of hepatitis E. The mode by which HEV attaches to and enters into target cells for productive infection remains unidentified. Open reading frame 2 (ORF2) of HEV encodes its major capsid protein, pORF2, which is likely to have the determinants for virus attachment and entry. Using an ∼56-kDa recombinant pORF2 that can self-assemble as virus-like particles, we demonstrated that cell surface heparan sulfate proteoglycans (HSPGs), specifically syndecans, play a crucial role in the binding of pORF2 to Huh-7 liver cells. Removal of cell surface heparan sulfate by enzymatic (heparinase) or chemical (sodium chlorate) treatment of cells or competition with heparin, heparan sulfate, and their oversulfated derivatives caused a marked reduction in pORF2 binding to the cells. Syndecan-1 is the most abundant proteoglycan present on these cells and, hence, plays a key role in pORF2 binding. Specificity is likely to be dictated by well-defined sulfation patterns on syndecans. We show that pORF2 binds syndecans predominantly via 6-O sulfation, indicating that binding is not entirely due to random electrostatic interactions. Using an in vitro infection system, we also showed a marked reduction in HEV infection of heparinase-treated cells. Our results indicate that, analogous to some enveloped viruses, a nonenveloped virus like HEV may have also evolved to use HSPGs as cellular attachment receptors.
22
Götte, Martin. "Syndecans in inflammation." FASEB Journal 17, no. 6 (April 2003): 575–91. http://dx.doi.org/10.1096/fj.02-0739rev.
Full text
23
Bobardt, Michael D., Udayan Chatterji, Suganya Selvarajah, Bernadette Van der Schueren, Guido David, Bruce Kahn, and Philippe A. Gallay. "Cell-Free Human Immunodeficiency Virus Type 1 Transcytosis through Primary Genital Epithelial Cells." Journal of Virology 81, no. 1 (October 18, 2006): 395–405. http://dx.doi.org/10.1128/jvi.01303-06.
Full textAbstract:
ABSTRACT Although the transport of human immunodeficiency virus type 1 (HIV-1) through the epithelium is critical for HIV-1 colonization, the mechanisms controlling this process remain obscure. In the present study, we investigated the transcellular migration of HIV-1 as a cell-free virus through primary genital epithelial cells (PGECs). The absence of CD4 on PGECs implicates an unusual entry pathway for HIV-1. We found that syndecans are abundantly expressed on PGECs and promote the initial attachment and subsequent entry of HIV-1 through PGECs. Although CXCR4 and CCR5 do not contribute to HIV-1 attachment, they enhance viral entry and transcytosis through PGECs. Importantly, HIV-1 exploits both syndecans and chemokine receptors to ensure successful cell-free transport through the genital epithelium. HIV-1-syndecan interactions rely on specific residues in the V3 of gp120 and specific sulfations within syndecans. We found no obvious correlation between coreceptor usage and the capacity of the virus to transcytose. Since viruses isolated after sexual transmission are mainly R5 viruses, this suggests that the properties conferring virus replication after transmission are distinct from those conferring cell-free virus transcytosis through the genital epithelium. Although we found that cell-free HIV-1 crosses PGECs as infectious particles, the efficiency of transcytosis is extremely poor (less than 0.02% of the initial inoculum). This demonstrates that the genital epithelium serves as a major barrier against HIV-1. Although one cannot exclude the possibility that limited passage of cell-free HIV-1 transcytosis through an intact genital epithelium occurs in vivo, it is likely that the establishment of infection via cell-free HIV-1 transmigration is a rare event.
24
Luyten, Annouck, Eva Mortier, Claude Van Campenhout, Vincent Taelman, Gisèle Degeest, Gunther Wuytens, Kathleen Lambaerts, Guido David, Eric J. Bellefroid, and Pascale Zimmermann. "The Postsynaptic Density 95/Disc-Large/Zona Occludens Protein Syntenin Directly Interacts with Frizzled 7 and Supports Noncanonical Wnt Signaling." Molecular Biology of the Cell 19, no. 4 (April 2008): 1594–604. http://dx.doi.org/10.1091/mbc.e07-08-0832.
Full textAbstract:
Wnt signaling pathways are essential for embryonic patterning, and they are disturbed in a wide spectrum of diseases, including cancer. An unresolved question is how the different Wnt pathways are supported and regulated. We previously established that the postsynaptic density 95/disc-large/zona occludens (PDZ) protein syntenin binds to syndecans, Wnt coreceptors, and known stimulators of protein kinase C (PKC)α and CDC42 activity. Here, we show that syntenin also interacts with the C-terminal PDZ binding motif of several Frizzled Wnt receptors, without compromising the recruitment of Dishevelled, a key downstream Wnt-signaling component. Syntenin is coexpressed with cognate Frizzled during early development in Xenopus. Overexpression and down-regulation of syntenin disrupt convergent extension movements, supporting a role for syntenin in noncanonical Wnt signaling. Syntenin stimulates c-jun phosphorylation and modulates Frizzled 7 signaling, in particular the PKCα/CDC42 noncanonical Wnt signaling cascade. The syntenin–Frizzled 7 binding mode indicates syntenin can accommodate Frizzled 7–syndecan complexes. We propose that syntenin is a novel component of the Wnt signal transduction cascade and that it might function as a direct intracellular link between Frizzled and syndecans.
25
Ding, Kan, Martha Lopez-Burks, José Antonio Sánchez-Duran, Murray Korc, and Arthur D. Lander. "Growth factor–induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells." Journal of Cell Biology 171, no. 4 (November 14, 2005): 729–38. http://dx.doi.org/10.1083/jcb.200508010.
Full textAbstract:
The cell surface heparan sulfate proteoglycan (HSPG) glypican-1 is up-regulated by pancreatic and breast cancer cells, and its removal renders such cells insensitive to many growth factors. We sought to explain why the cell surface HSPG syndecan-1, which is also up-regulated by these cells and is a known growth factor coreceptor, does not compensate for glypican-1 loss. We show that the initial responses of these cells to the growth factor FGF2 are not glypican dependent, but they become so over time as FGF2 induces shedding of syndecan-1. Manipulations that retain syndecan-1 on the cell surface make long-term FGF2 responses glypican independent, whereas those that trigger syndecan-1 shedding make initial FGF2 responses glypican dependent. We further show that syndecan-1 shedding is mediated by matrix metalloproteinase-7 (MMP7), which, being anchored to cells by HSPGs, also causes its own release in a complex with syndecan-1 ectodomains. These results support a specific role for shed syndecan-1 or MMP7–syndecan-1 complexes in tumor progression and add to accumulating evidence that syndecans and glypicans have nonequivalent functions in vivo.
26
Okayama, Minoru, Seiichi Munesue, Masato Komaki, Yuri Kusano, and Kayoko Oguri. "Functional Specificity of Syndecans." Trends in Glycoscience and Glycotechnology 10, no. 52 (1998): 211–21. http://dx.doi.org/10.4052/tigg.10.211.
Full text
27
Lunde, Ida G., Kate M. Herum, Cathrine C. Carlson, and Geir Christensen. "Syndecans in heart fibrosis." Cell and Tissue Research 365, no. 3 (July 14, 2016): 539–52. http://dx.doi.org/10.1007/s00441-016-2454-2.
Full text
28
Beauvais, DeannaLee M., Brandon J. Burbach, and Alan C. Rapraeger. "The syndecan-1 ectodomain regulates αvβ3 integrin activity in human mammary carcinoma cells." Journal of Cell Biology 167, no. 1 (October 11, 2004): 171–81. http://dx.doi.org/10.1083/jcb.200404171.
Full textAbstract:
The αvβ3 integrin participates in cell morphogenesis, growth factor signaling, and cell survival. Activation of the integrin is central to these processes and is influenced by specific ECM components, which engage both integrins and syndecans. This paper demonstrates that the αvβ3 integrin and syndecan-1 (S1) are functionally coupled. The integrin is dependent on the syndecan to become activated and to mediate signals required for MDA-MB-231 and MDA-MB-435 human mammary carcinoma cell spreading on vitronectin or S1-specific antibody. Coupling of the syndecan to αvβ3 requires the S1 ectodomain (ED), as ectopic expression of glycosylphosphatidylinositol-linked S1ED enhances αvβ3 recognition of vitronectin; and treatments that target this domain, including competition with recombinant S1ED protein or anti-S1ED antibodies, mutation of the S1ED, or down-regulation of S1 expression by small-interfering RNAs, disrupt αvβ3-dependent cell spreading and migration. Thus, S1 is likely to be a critical regulator of many cellular behaviors that depend on activated αvβ3 integrins.
29
Baciu, P. C., and P. F. Goetinck. "Protein kinase C regulates the recruitment of syndecan-4 into focal contacts." Molecular Biology of the Cell 6, no. 11 (November 1995): 1503–13. http://dx.doi.org/10.1091/mbc.6.11.1503.
Full textAbstract:
Cell surface heparan sulfate proteoglycans have been implicated as co-receptors facilitating cell adhesion and growth factor binding. Recent studies on the role of a family of transmembrane heparan sulfate proteoglycans, syndecans, in cell adhesion has identified one member, syndecan-4, to be present within focal contacts. The current study investigates the mechanisms regulating the association of syndecan-4 with focal contacts based upon its immunolocalization with vinculin in quiescent, serum-stimulated, and 12-0-tetradecanoylphorbol 13-acetate (TPA)-induced cultures. In quiescent cells, syndecan-4 did not localize to focal contacts. However, activation of protein kinase C by TPA or serum induces the active recruitment of syndecan-4 into focal contacts. This induction preferentially localizes syndecan-4 to focal contacts behind the leading lamella, the subnuclear region, and along the trailing edge of migratory cells. Focal contacts in either freshly adhered cells or in the leading lamellae of migrating cells did not stain for syndecan-4. In addition to the observed subcellular distribution and recruitment, syndecan-4 was observed to co-localize with endogenously synthesized fibronectin fibrils within focal contacts as well as with fibrils present in the matrix. These findings suggest that protein kinase C activation results in syndecan-4 recruitment to focal contacts and its association with sites of matrix deposition.
30
Ridley, RC, H. Xiao, H. Hata, J. Woodliff, J. Epstein, and RD Sanderson. "Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen." Blood 81, no. 3 (February 1, 1993): 767–74. http://dx.doi.org/10.1182/blood.v81.3.767.767.
Full textAbstract:
Abstract The syndecans comprise a family of integral membrane proteoglycans that regulate cell behaviors by binding to extracellular matrix and binding growth factors. In mouse blood cells, syndecan expression is restricted to cells of the B-cell lineage where it is expressed by pre-B cells and plasma cells, but is absent from circulating B cells. In the present study, we examined the expression, structure, and function of syndecan on human myeloma cell lines and myeloma patient bone marrow cells. On myeloma cells, syndecan is a small (modal relative molecular mass [M(r)] = 120 Kd) heparan sulfate proteoglycan localized at the cell surface. Syndecan was detected by immunodot blotting on 7 of 10 human myeloma cell lines and by reverse transcriptase polymerase chain reaction on 10 of 14 patient samples. Cell binding assays show that myeloma cells expressing syndecan bind to type I collagen via heparan sulfate chains, while those cell lines not expressing syndecan do not bind to collagen. Furthermore, the cell lines expressing syndecan were negative for CD19 and CD45 staining, indicating that syndecan expression is restricted to tumors having a well-differentiated phenotype. We conclude that syndecan acts as a matrix receptor on human myeloma cells but is not expressed by all tumors, suggesting that syndecan may participate in regulating myeloma cell adhesion to the bone marrow stromal matrix.
31
Ridley, RC, H. Xiao, H. Hata, J. Woodliff, J. Epstein, and RD Sanderson. "Expression of syndecan regulates human myeloma plasma cell adhesion to type I collagen." Blood 81, no. 3 (February 1, 1993): 767–74. http://dx.doi.org/10.1182/blood.v81.3.767.bloodjournal813767.
Full textAbstract:
The syndecans comprise a family of integral membrane proteoglycans that regulate cell behaviors by binding to extracellular matrix and binding growth factors. In mouse blood cells, syndecan expression is restricted to cells of the B-cell lineage where it is expressed by pre-B cells and plasma cells, but is absent from circulating B cells. In the present study, we examined the expression, structure, and function of syndecan on human myeloma cell lines and myeloma patient bone marrow cells. On myeloma cells, syndecan is a small (modal relative molecular mass [M(r)] = 120 Kd) heparan sulfate proteoglycan localized at the cell surface. Syndecan was detected by immunodot blotting on 7 of 10 human myeloma cell lines and by reverse transcriptase polymerase chain reaction on 10 of 14 patient samples. Cell binding assays show that myeloma cells expressing syndecan bind to type I collagen via heparan sulfate chains, while those cell lines not expressing syndecan do not bind to collagen. Furthermore, the cell lines expressing syndecan were negative for CD19 and CD45 staining, indicating that syndecan expression is restricted to tumors having a well-differentiated phenotype. We conclude that syndecan acts as a matrix receptor on human myeloma cells but is not expressed by all tumors, suggesting that syndecan may participate in regulating myeloma cell adhesion to the bone marrow stromal matrix.
32
Couchman, John R. "Syndecan-1 (CD138), Carcinomas and EMT." International Journal of Molecular Sciences 22, no. 8 (April 19, 2021): 4227. http://dx.doi.org/10.3390/ijms22084227.
Full textAbstract:
Cell surface proteoglycans are known to be important regulators of many aspects of cell behavior. The principal family of transmembrane proteoglycans is the syndecans, of which there are four in mammals. Syndecan-1 is mostly restricted to epithelia, and bears heparan sulfate chains that are capable of interacting with a large array of polypeptides, including extracellular matrix components and potent mediators of proliferation, adhesion and migration. For this reason, it has been studied extensively with respect to carcinomas and tumor progression. Frequently, but not always, syndecan-1 levels decrease as tumor grade, stage and invasiveness and dedifferentiation increase. This parallels experiments that show depletion of syndecan-1 can be accompanied by loss of cadherin-mediated adhesion. However, in some tumors, levels of syndecan-1 increase, but the characterization of its distribution is relevant. There can be loss of membrane staining, but acquisition of cytoplasmic and/or nuclear staining that is abnormal. Moreover, the appearance of syndecan-1 in the tumor stroma, either associated with its cellular component or the collagenous matrix, is nearly always a sign of poor prognosis. Given its relevance to myeloma progression, syndecan-1-directed antibody—toxin conjugates are being tested in clinical and preclinical trials, and may have future relevance to some carcinomas.
33
Hudák, Anett, Gareth Morgan, Jaromir Bacovsky, Roland Patai, Tamás F. Polgár, Annamária Letoha, Aladar Pettko-Szandtner, Csaba Vizler, László Szilák, and Tamás Letoha. "Biodistribution and Cellular Internalization of Inactivated SARS-CoV-2 in Wild-Type Mice." International Journal of Molecular Sciences 23, no. 14 (July 9, 2022): 7609. http://dx.doi.org/10.3390/ijms23147609.
Full textAbstract:
Despite the growing list of identified SARS-CoV-2 receptors, the human angiotensin-converting enzyme 2 (ACE2) is still viewed as the main cell entry receptor mediating SARS-CoV-2 internalization. It has been reported that wild-type mice, like other rodent species of the Muridae family, cannot be infected with SARS-CoV-2 due to differences in their ACE2 receptors. On the other hand, the consensus heparin-binding motif of SARS-CoV-2’s spike protein, PRRAR, enables the attachment to rodent heparan sulfate proteoglycans (HSPGs), including syndecans, a transmembrane HSPG family with a well-established role in clathrin- and caveolin-independent endocytosis. As mammalian syndecans possess a relatively conserved structure, we analyzed the cellular uptake of inactivated SARS-CoV-2 particles in in vitro and in vivo mice models. Cellular studies revealed efficient uptake into murine cell lines with established syndecan-4 expression. After intravenous administration, inactivated SARS-CoV-2 was taken up by several organs in vivo and could also be detected in the brain. Internalized by various tissues, inactivated SARS-CoV-2 raised tissue TNF-α levels, especially in the heart, reflecting the onset of inflammation. Our studies on in vitro and in vivo mice models thus shed light on unknown details of SARS-CoV-2 internalization and help broaden the understanding of the molecular interactions of SARS-CoV-2.
34
Hozumi, Kentaro, Nobuharu Suzuki, Peter K. Nielsen, Motoyoshi Nomizu, and Yoshihiko Yamada. "Laminin α1 Chain LG4 Module Promotes Cell Attachment through Syndecans and Cell Spreading through Integrin α2β1." Journal of Biological Chemistry 281, no. 43 (August 30, 2006): 32929–40. http://dx.doi.org/10.1074/jbc.m605708200.
Full textAbstract:
The laminin α1 chain is a subunit of laminin-1, a heterotrimeric basement membrane protein. The LG4-5 module at the C terminus of laminin α1 contains major binding sites for heparin, sulfatide, and α-dystroglycan and plays a critical role in early embryonic development. We previously identified active synthetic peptides AG73 and EF-1 from the sequence of lamininα1 LG4 for binding to syndecan and integrin α2β1, respectively. However, their activity and functional relationship within the laminin-1 and LG4 as well as the functional relation between these sites and α-dystroglycan binding sites in LG4 are not clear. To address these questions, we created mutant recombinant LG4 proteins containing alanine substitutions within the AG73 (M1), EF-1 (M2, M3), and α-dystroglycan binding sites (M4, M5) and analyzed their activities. We found that recombinant proteins rec-M1 and rec-M5, containing mutations within M1 and M5, respectively, did not bind heparin or lymphoid cell lines expressing syndecans. These results suggest that LG4 binds to heparin and syndecans through M1 and M5. Rec-M1 and rec-M5 reduced fibroblast attachment, whereas mutant rec-M2 and rec-M3 retained cell attachment activity but did not promote cell spreading. Fibroblast attachment to rec-LG4 was inhibited by heparin but not by integrin antibodies. Spreading of fibroblasts on rec-LG4 was inhibited by anti-integrin α2 and β1 but not by anti-integrin α1 and α6. These results suggest that the M1 and M5 sites are necessary for cell attachment on LG4 through syndecans and that the EF-1 site is for cell spreading activity through integrin α2β1. In contrast, laminin-1-mediated fibroblast attachment and spreading were not inhibited by heparin or antiintegrin α2. Our findings indicate that LG4 has a unique function distinct from laminin-1 and suggest that laminin α1 LG4-5 may also be produced by a proteolytic cleavage in certain tissues where it exerts its activity.
35
Nasi, S., J. Bertrand, M. Bollmann, R. Stange, and T. Pap. "THU0435 CALCIUM PYROPHOSPHATE DIHYDRATE (CPPD) CRYSTALS BUT NOT BASIC CALCIUM PHOSPHATE (BCP) CRYSTALS INDUCE SYNDECAN-4 EXPRESSION IN CARTILAGE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 454.2–455. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2772.
Full textAbstract:
Background:Chondrocalcinosis is a painful rheumatic condition caused by the deposition of calcium pyrophosphate dihydrate crystals (CPPD) in joint tissues, and especially in cartilage. It is known that CPPD crystals cause inflammation and degenerative changes in joint, but the underlying mechanisms remain poorly understood. In particular, nothing is known about how these crystals regulates transmembrane heparan sulphate proteoglycans (HSPGs). Our attention focused on one family of HSPGs called syndecans as they have important roles both as adhesion molecules, by mediating chondrocyte-extracellular matrix interactions, and as modulators of intracellular signaling triggered by cytokines and growth factors.Objectives:The aim of this study was to evaluate how CPPD crystals modulates syndecan expression in chondrocytes and in cartilage, and how this modulation can be ultimately linked to cartilage damage during chondrocylcinosis.Methods:Murine chondrocitic ATDC5 cells were stimulated with 0,1 ng/ml CPPD crystals or with 0,1 ng/ml basic-calcium phosphate crystals (BCP), a family of calcium-containing crystals found in other rheumatic conditions such as osteoarthritis (OA). Cytotoxicity was evaluated by lactate dehydrogenase (LDH) release in the supernatant at 30 minutes, and 3, 6, 24 hours after stimulation. At the same time-points, mRNA expression levels of syndecans (Synd-1, -2, -3, -4) and of matrix-degrading enzymes (Mmp-3, -9, -13; Adamts-4, -5) was analysed by qRT-PCR. Finally, Syndecan-4 protein expression was studied by immunohistochemistry (IHC) in cartilage samples of patients with chondrocalcinosis and in samples of patients with severe OA without chondrocalcinosis as control.Results:LDH assay revealed no increased cytotoxicity by CPPD or BCP at any time-point. qRT-PCR indicated that CPPD crystals but not BCP crystals induced Synd-2 and -3 upregulation at 30 minutes after stimulation and Synd-4 upregulation at 3 hours, while no modulation of syndecans was seen at later time-points. CPPD also induced Adamts-4 expression at 3 hours after stimulation, and Mmp-9 expression at 3 and 6 hours. The expression of the other matrix-degrading enzymes was not affected. Human chondrocalcinosis cartilage exhibited enhanced Synd-4 expression compared to severe OA cartilage containing BCP calcification. Interestingly, Synd-4 expression was observed in the extracellular matrix but not on cell membrane, suggesting that maybe Synd-4 undergoes shedding (Figure 1).Figure 1.Representative Synd-4 IHC in control patients (Ctrl, severe OA) and chondrocalcinosis patients (CPPD). Note increased Synd-4 expression in extracellular matrix of CPPD patients compared to Ctrl ones.Conclusion:BCP and CPPD crystals seem to trigger differential effects in terms of modulation of syndecans in chondrocitic cells. CPPD crystals induce Synd-4 and Adamts-4 and Mmp-9 which are not induced by BCP crystals. It remains to be clarified whether the two events are interlinked. In particular, further studies are required to investigate if Adamts-4 and Mmp-9 are involved in Synd-4 shedding or if vice versa Synd-4 regulates Adamts-4 and Mmp-9 activation and downstream cartilage breakdown in chondrocalcinosis.Disclosure of Interests: :Sonia Nasi: None declared, Jessica Bertrand Grant/research support from: Pfizer, Speakers bureau: Pfizer, Miriam Bollmann: None declared, Richard Stange: None declared, Thomas Pap: None declared
36
Yamashita, Yoshio, Kenji Oritani, Erina K. Miyoshi, Randolph Wall, Merton Bernfield, and Paul W. Kincade. "Syndecan-4 Is Expressed by B Lineage Lymphocytes and Can Transmit a Signal for Formation of Dendritic Processes." Journal of Immunology 162, no. 10 (May 15, 1999): 5940–48. http://dx.doi.org/10.4049/jimmunol.162.10.5940.
Full textAbstract:
Abstract Our previous studies indicated that stromal cell-derived syndecan-4 might mediate some form of communication with pre-B cells in bone marrow. We now report additional aspects of this recognition and show that syndecan-4 is also present on pre-B cells. Indeed, the molecule is acquired at an early stage of differentiation and retained until mature B cells undergo Ig isotype switching. mAbs developed to two portions of the syndecan-4 protein core were used to probe possible functions on B lineage lymphocytes. Syndecan-4 ligation had no obvious influence on B lymphocyte formation or activation, but this treatment caused a dramatic morphological change in appropriately stimulated leukocytes. Extended filopodia appeared on transfected Ba/F3 or FDCP-1 cells, as well as activated B cell blasts that were placed on syndecan-4 Ab-coated surfaces. The dendritic processes contained polymerized actin as well as pp52(LSP1), a prominent F-actin binding protein in lymphocytes. The cytoplasmic domain of syndecan-4 was not required for this response. Shape changes of this type could facilitate interactions between B lymphocytes and other components of the immune system. Not only is syndecan-4 a useful marker for discriminating normal B lineage lymphocyte subsets, but our results suggest new ways for the syndecans to participate in immune responses.
37
Kopper, László. "Syndecans and the Lymphoid System." Leukemia & Lymphoma 38, no. 3-4 (January 2000): 271–81. http://dx.doi.org/10.3109/10428190009087018.
Full text
38
Nelson, Axel, Joakim Johansson, Jonas Tydén, and Mikael Bodelsson. "Circulating syndecans during critical illness." APMIS 125, no. 5 (March 3, 2017): 468–75. http://dx.doi.org/10.1111/apm.12662.
Full text
39
Romarı́s, Manuel, Christien Coomans, Helga Ceulemans, Anne-Mie Bruystens, Sylvie Vekemans, and Guido David. "Molecular Polymorphism of the Syndecans." Journal of Biological Chemistry 274, no. 26 (June 25, 1999): 18667–74. http://dx.doi.org/10.1074/jbc.274.26.18667.
Full text
40
Gallay, Philippe. "Syndecans and HIV-1 pathogenesis." Microbes and Infection 6, no. 6 (May 2004): 617–22. http://dx.doi.org/10.1016/j.micinf.2004.02.004.
Full text
41
Letoha, Tamás, Anikó Keller-Pintér, Erzsébet Kusz, Csongor Kolozsi, Zsolt Bozsó, Gábor Tóth, Csaba Vizler, Zoltán Oláh, and László Szilák. "Cell-penetrating peptide exploited syndecans." Biochimica et Biophysica Acta (BBA) - Biomembranes 1798, no. 12 (December 2010): 2258–65. http://dx.doi.org/10.1016/j.bbamem.2010.01.022.
Full text
42
Gondelaud, Frank, and Sylvie Ricard‐Blum. "Structures and interactions of syndecans." FEBS Journal 286, no. 15 (April 8, 2019): 2994–3007. http://dx.doi.org/10.1111/febs.14828.
Full text
43
Couchman, John R., and Anne Woods. "Syndecans, signaling, and cell adhesion." Journal of Cellular Biochemistry 61, no. 4 (June 16, 1996): 578–84. http://dx.doi.org/10.1002/(sici)1097-4644(19960616)61:4<578::aid-jcb11>3.0.co;2-c.
Full text
44
Carey, DJ, RC Stahl, G. Cizmeci-Smith, and VK Asundi. "Syndecan-1 expressed in Schwann cells causes morphological transformation and cytoskeletal reorganization and associates with actin during cell spreading." Journal of Cell Biology 124, no. 1 (January 1, 1994): 161–70. http://dx.doi.org/10.1083/jcb.124.1.161.
Full textAbstract:
To investigate the biological functions of transmembrane proteoglycans we have produced clonal cell lines of rat Schwann cells that express the hybrid proteoglycan syndecan-1. This was done by transfection of newborn rat Schwann cells with a plasmid vector bearing the rat syndecan-1 cDNA sequence under transcriptional control of the constitutively active cytomegalovirus promoter, and a neomycin resistance gene. Stably expressing cells were selected by growth in G418. Expression of syndecan-1 was verified by Northern and immunoblot analysis and immunoprecipitation of 35SO4-labeled proteoglycans. The syndecan-1 expressing cells exhibited significantly enhanced spreading on several different substrata, including fibronectin and laminin, and an altered morphology. The enhanced spreading appeared to result from the presence of syndecan-1, based on the observation that anti-syndecan-1 antibodies inhibited the enhanced substratum spreading. There was also a reorganization of cytoskeletal structures and formation of focal adhesions, visualized by anti-vinculin staining, which were absent from control Schwann cells. There was no apparent stable association of cell surface syndecan-1 with focal contact sites, as determined by dual staining with anti-syndecan-1 and anti-vinculin antibodies. Colocalization of patches of cell surface syndecan-1 with actin was observed, but only during cell spreading. These findings provide evidence for a role of transmembrane proteoglycans in cellular morphogenesis, and suggest that transient association of syndecans with microfilaments may be an important aspect of their biological function.
45
CHEN, Ligong, John R. COUCHMAN, Jacqueline SMITH, and Anne WOODS. "Molecular characterization of chicken syndecan-2 proteoglycan." Biochemical Journal 366, no. 2 (September 1, 2002): 481–90. http://dx.doi.org/10.1042/bj20020711.
Full textAbstract:
A partial syndecan-2 sequence (147bp) was obtained from chicken embryonic fibroblast poly(A)+ RNA by reverse transcription–PCR. This partial sequence was used to produce a 5′-end-labelled probe. A chicken liver cDNA library was screened with this probe, and overlapping clones were obtained encompassing the entire cDNA of 3kb. The open reading frame encodes a protein of 201 amino acids. The cytoplasmic domain is identical with that of mammalian syndecan-2, and highly similar to those of Xenopus laevis and zebrafish syndecan-2. The transmembrane domain is identical with that of mammalian and zebrafish syndecan-2, and highly similar to that of Xenopus laevis syndecan-2. The ectodomain is 45–62% identical with that of zebrafish, Xenopus laevis and mammalian syndecan-2. Two coding single nucleotide polymorphisms were observed. In vitro transcription and translation yielded a product of 30kDa. Western blotting of chicken embryonic fibroblast cell lysates with species-specific monoclonal antibody mAb 8.1 showed that chicken syndecan-2 is substituted with heparan sulphate, and that the major form of chicken syndecan-2 isolated from chicken fibroblasts is consistent with the formation of SDS-resistant dimers, which is common for syndecans. A 5′-end-labelled probe hybridized to two mRNA species in chicken embryonic fibroblasts, while Northern analysis with poly(A)+ RNAs from different tissues of chicken embryos showed wide and distinct distributions of chicken syndecan-2 during embryonic development. This pattern was different from that reported for syndecan-4, but consistent with the roles of syndecan-2 in neural maturation and in mesenchymal–matrix interactions.
46
Steinfeld, R., H. Van Den Berghe, and G. David. "Stimulation of fibroblast growth factor receptor-1 occupancy and signaling by cell surface-associated syndecans and glypican." Journal of Cell Biology 133, no. 2 (April 15, 1996): 405–16. http://dx.doi.org/10.1083/jcb.133.2.405.
Full textAbstract:
The formation of distinctive basic FGF-heparan sulfate complexes is essential for the binding of bFGF to its cognate receptor. In previous experiments, cell-surface heparan sulfate proteoglycans extracted from human lung fibroblasts could not be shown to promote high affinity binding of bFGF when added to heparan sulfate-deficient cells that express FGF receptor-1 (FGFR1) (Aviezer, D., D. Hecht, M. Safran, M. Eisinger, G. David, and A. Yayon. 1994. Cell 79:1005-1013). In alternative tests to establish whether cell-surface proteoglycans can support the formation of the required complexes, K562 cells were first transfected with the IIIc splice variant of FGFR1 and then transfected with constructs coding for either syndecan-1, syndecan-2, syndecan-4 or glypican, or with an antisense syndecan-4 construct. Cells cotransfected with receptor and proteoglycan showed a two- to three- fold increase in neutral salt-resistant specific 125I-bFGF binding in comparison to cells transfected with only receptor or cells cotransfected with receptor and anti-syndecan-4. Exogenous heparin enhanced the specific binding and affinity cross-linking of 125I-bFGF to FGFR1 in receptor transfectants that were not cotransfected with proteoglycan, but had no effect on this binding and decreased the yield of bFGFR cross-links in cells that were cotransfected with proteoglycan. Receptor-transfectant cells showed a decrease in glycophorin A expression when exposed to bFGF. This suppression was dose-dependent and obtained at significantly lower concentrations of bFGF in proteoglycan-cotransfected cells. Finally, complementary cell-free binding assays indicated that the affinity of 125I-bFGF for an immobilized FGFR1 ectodomain was increased threefold when the syndecan-4 ectodomain was coimmobilized with receptor. Equimolar amounts of soluble syndecan-4 ectodomain, in contrast, had no effect on this binding. We conclude that, at least in K562 cells, syndecans and glypican can support bFGF-FGFR1 interactions and signaling, and that cell-surface association may augment their effectiveness.
47
SCHOFIELD, Karen P., John T. GALLAGHER, and Guido DAVID. "Expression of proteoglycan core proteins in human bone marrow stroma." Biochemical Journal 343, no. 3 (October 25, 1999): 663–68. http://dx.doi.org/10.1042/bj3430663.
Full textAbstract:
Heparan sulphate proteoglycans (HSPGs) present on the surface of bone marrow stromal cells and in the extracellular matrix (ECM) have important roles in the control of adhesion and growth of haemopoietic stem and progenitor cells. The two main groups of proteoglycans which contain heparan sulphate chains are members of the syndecan and glypican families. In this study we have identified the main surface membrane and matrix-associated HSPGs present in normal human bone marrow stroma formed in long-term culture. Proteoglycans were extracted from the adherent stromal layers and treated with heparitinase and chondroitinase ABC. The core proteins were detected by Western blotting using antibodies directed against syndecans-1-4, glypican-1 and the ECM HSPG, perlecan. Stromal cell expression at the RNA level was detected by Northern blotting and by reverse transcription PCR. Glypican-1, syndecan-3 and syndecan-4 were the major cell-membrane HSPG species and perlecan was the major ECM proteoglycan. There was no evidence for expression of syndecan-1 protein. Syndecan-3 was expressed mainly as a variant or processed 50-55 kDa core protein and in lower amounts as the characteristic 125 kDa core protein. These results suggest that syndecan-3, syndecan-4 and glypican-1 present on the surface of marrow stromal cells, together with perlecan in the ECM, may be responsible for creating the correct stromal ‘niche’ for the maintenance and development of haemopoietic stem and progenitor cells. The detection of a variant form of syndecan-3 as a major stromal HSPG suggests a specific role for this syndecan in haemopoiesis.
48
Chappell, Daniel, Matthias Jacob, Markus Rehm, Mechthild Stoeckelhuber, Ulrich Welsch, Peter Conzen, and Bernhard F. Becker. "Heparinase selectively sheds heparan sulphate from the endothelial glycocalyx." Biological Chemistry 389, no. 1 (January 1, 2008): 79–82. http://dx.doi.org/10.1515/bc.2008.005.
Full textAbstract:
Abstract A healthy vascular endothelium is coated by the endothelial glycocalyx. Its main constituents are transmembrane syndecans and bound heparan sulphates. This structure maintains the physiological endothelial permeability barrier and prevents leukocyte and platelet adhesion, thereby mitigating inflammation and tissue oedema. Heparinase, a bacterial analogue to heparanase, is known to attack the glycocalyx. However, the exact extent and specificity of degradation is unresolved. We show by electron microscopy, immunohistological staining and quantitative measurements of the constituent parts, that heparinase selectively sheds heparan sulphate from the glycocalyx, but not the syndecans.
49
Teel, A. L., and H. J. Yost. "Embryonic expression patterns of Xenopus syndecans." Mechanisms of Development 59, no. 2 (October 1996): 115–27. http://dx.doi.org/10.1016/0925-4773(96)00584-9.
Full text
50
Woods, Anne, and John R. Couchman. "Syndecans: synergistic activators of cell adhesion." Trends in Cell Biology 8, no. 5 (May 1998): 189–92. http://dx.doi.org/10.1016/s0962-8924(98)01244-6.
Full text