Academic literature on the topic 'Microtubuli'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Microtubuli.'
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.
Journal articles on the topic "Microtubuli"
1
Vollrath, Michael, and Michael Altmannsberger. "Chemically Induced Esthesioneuroepithelioma: Ultrastructural Findings." Annals of Otology, Rhinology & Laryngology 98, no. 4 (1989): 256–66. http://dx.doi.org/10.1177/000348948909800404.
Full textAbstract:
Tumors of the olfactory epithelium of rats were induced with two different nitrosamines: 2,6-dimethylnitrosomorpholine and N-nitrosopiperidine. Both carcinogens yielded identical tumors consisting of small, undifferentiated, neuroblastic cell elements without specialized cell contact. Cell processes contained microtubuli, centrioles, and neurosecretory granules. Two kinds of rosettes were encountered frequently: Neuroblastic Homer Wright rosettes consisted of undifferentiated cells, surrounding a minute lumen filled with amorphous material; and Flexner rosettes showed a higher degree of maturation. Inside their central lumen, cell processes with characteristic features of olfactory sensory cells (basal bodies, cilia, centrioles, microtubuli) could be demonstrated. The stem cell of this tumor is most likely the undifferentiated light basal cell inside the olfactory epithelium, since its ultrastructural appearance and its cytoskeleton are alike. At least under neoplastic conditions, this stem cell may likewise differentiate into epithelial cells, since transition to squamous cell carcinomas has been observed. In view of their overwhelming similarity to their human counterpart, the induced tumors are most likely to represent esthesioneuroepitheliomas.
2
Teng, Miao, Yong-Ming Dang, Jia-ping Zhang та ін. "Microtubular stability affects cardiomyocyte glycolysis by HIF-1α expression and endonuclear aggregation during early stages of hypoxia". American Journal of Physiology-Heart and Circulatory Physiology 298, № 6 (2010): H1919—H1931. http://dx.doi.org/10.1152/ajpheart.01039.2009.
Full textAbstract:
Hypoxia-inducible factor (HIF)-1α is a key regulator of anaerobic energy metabolism. We asked the following question: Does the breakdown of microtubular structures influence glycolysis in hypoxic cardiomyocytes by regulating HIF-1α? Neonatal rat cardiomyocytes were cultured under hypoxic conditions, while microtubule-stabilizing (paclitaxel) and -depolymerizing (colchicine) agents were used to change microtubular structure. Models of high microtubule-associated protein 4 (MAP4) expression and RNA interference of microtubulin expression were established. Microtubular structural changes and intracellular HIF-1α protein distribution were observed with laser confocal scanning microscopy. Content of key glycolytic enzymes, viability, and energy content of cardiomyocytes were determined by colorimetry and high-performance liquid chromatography. HIF-1α protein content and mRNA expression were determined by Western blotting and real-time PCR, respectively. Low doses of microtubule-stabilizing agent (10 μmol/l paclitaxel) and enhanced expression of MAP4 stabilized the reticular microtubular structures in hypoxic cardiomyocytes, increased the content of key glycolytic enzymes, ameliorated energy supply and enhanced cell viability, and upregulated HIF-1α protein expression and endonuclear aggregation. In contrast, the microtubule-depolymerizing agent (10 μmol/l colchicine) or reduced microtubulin expression had adverse affects on the same parameters, in particular, HIF-1α protein content and endonuclear aggregation. We conclude that microtubular structural changes influence glycolysis in the early stages of hypoxia in cardiomyocytes by regulating HIF-1α content. Stabilizing microtubular structures increases endonuclear and total HIF-1α expression, content of key glycolytic enzymes, and energy supply. These findings provide potential therapeutic targets for ameliorating cell energy metabolism during early myocardial hypoxia.
3
Theron, J. J., H. Bosman, R. De Winter, and C. N. Henning. "Sekresiemeganisme van atriale natriuretiese peptied (ANP)." Suid-Afrikaanse Tydskrif vir Natuurwetenskap en Tegnologie 12, no. 2 (1993): 37–39. http://dx.doi.org/10.4102/satnt.v12i2.557.
Full textAbstract:
Mechanical stretch of atrial muscle in vitro induces movement of ANP granules from central perinuclear areas to the periphery of the sarcoplasm at the sarcolemma. This centrifugal movement is associated with maximal secretion of ANP into the suspension medium, without morphological evidence of exocytosis. Since the addition of vinblastine suppresses the movement of granules and ANP secretion, microtubuli are probably involved in the intracellular movement of ANP granules.
4
Ookata, K., S. Hisanaga, E. Okumura, and T. Kishimoto. "Association of p34cdc2/cyclin B complex with microtubules in starfish oocytes." Journal of Cell Science 105, no. 4 (1993): 873–81. http://dx.doi.org/10.1242/jcs.105.4.873.
Full textAbstract:
The microtubular cytoskeleton exhibits a dramatic reorganization, progressing from interphase radial arrays to a mitotic spindle at the G2/M transition. Although this reorganization has been suspected to be caused by maturation promoting factor (MPF: p34cdc2/cyclin B complex), little is known about how p34cdc2 kinase controls microtubule networks. We provide evidence of the direct association of the p34cdc2/cyclin B complex with microtubules in starfish oocytes. Anti-cyclin B staining of detergent-treated oocytes, isolated asters and meiotic spindles revealed fluorescence associated with microtubule fibers, chromosomes and centrosomes. Microtubules prepared from starfish oocytes were associated with cyclin B and p34cdc2 proteins. Microtubule-bound p34cdc2 and cyclin B were released from microtubules by a high-salt solution and possessed a complex form as shown by the adsorption to suc1-beads and by immunoprecipitation with the anti-cyclin B antibody. The p34cdc2/cyclin B complex associated to microtubules had high histone H1 kinase activity at meiotic metaphase. However, it was not necessary for the p34cdc2/cyclin B complex to be active for microtubule binding, as an inactive form in immature oocytes was also observed to bind to microtubules. The coprecipitation of suc1-column purified p34cdc2/cyclin B with purified porcine brain microtubules in the presence of starfish oocyte microtubule-associated proteins (MAPs) indicates that the association of p34cdc2/cyclin B with microtubules in vitro is mediated by MAPs.
5
Bajer, A. S., and J. Molè-Bajer. "Reorganization of microtubules in endosperm cells and cell fragments of the higher plant Haemanthus in vivo." Journal of Cell Biology 102, no. 1 (1986): 263–81. http://dx.doi.org/10.1083/jcb.102.1.263.
Full textAbstract:
The reorganization of the microtubular meshwork was studied in intact Haemanthus endosperm cells and cell fragments (cytoplasts). This higher plant tissue is devoid of a known microtubule organizating organelle. Observations on living cells were correlated with microtubule arrangements visualized with the immunogold method. In small fragments, reorganization did not proceed. In medium and large sized fragments, microtubular converging centers formed first. Then these converging centers reorganized into either closed bushy microtubular spiral or chromosome-free cytoplasmic spindles/phragmoplasts. Therefore, the final shape of organized microtubular structures, including spindle shaped, was determined by the initial size of the cell fragments and could be achieved without chromosomes or centrioles. Converging centers elongate due to the formation of additional structures resembling microtubular fir trees. These structures were observed at the pole of the microtubular converging center in anucleate fragments, accessory phragmoplasts in nucleated cells, and in the polar region of the mitotic spindle during anaphase. Therefore, during anaphase pronounced assembly of new microtubules occurs at the polar region of acentriolar spindles. Moreover, statistical analysis demonstrated that during the first two-thirds of anaphase, when chromosomes move with an approximately constant speed, kinetochore fibers shorten, while the length of the kinetochore fiber complex remains constant due to the simultaneous elongation of their integral parts (microtubular fir trees). The half-spindle shortens only during the last one-third of anaphase. These data contradict the presently prevailing view that chromosome-to-pole movements in acentriolar spindles of higher plants are concurrent with the shortening of the half-spindle, the self-reorganizing property of higher plant microtubules (tubulin) in vivo. It may be specific for cells without centrosomes and may be superimposed also on other microtubule-related processes.
6
Buljan, Vlado A., Manuel B. Graeber, R. M. Damian Holsinger, et al. "Calcium–axonemal microtubuli interactions underlie mechanism(s) of primary cilia morphological changes." Journal of Biological Physics 44, no. 1 (2017): 53–80. http://dx.doi.org/10.1007/s10867-017-9475-2.
Full text
7
Roychoudhury, Sonali, and Martha J. Powell. "Ultrastructure of mitosis in the algal parasitic fungus Polyphagus euglenae." Canadian Journal of Botany 69, no. 10 (1991): 2201–14. http://dx.doi.org/10.1139/b91-277.
Full textAbstract:
Ultrastructure of mitosis in the parasitic fungus, Polyphagus euglenae, was investigated with emphasis on centrosome structure and prophase events. The interphase centrosome included a diplosome, scattered electron-dense satellites, and multiple ring-shaped microtubule foci. As centrosomes separated during prophase, microtubular arrays extended between the replicated centrosomes and radiated out along the outer surface of the nuclear envelope. The asymmetric configuration of these microtubular arrays suggests that intersecting microtubules provide tension forces on elongating centrosome to centrosome microtubules during centrosome separation. After centrosome migration, multiple microtubule foci appeared to fuse into crescent-shaped microtubule organizing centers. Condensing chromatin was concentrated in the region of the future equatorial plane of the mitotic spindle prior to the appearance of discontinuities in the nuclear envelope and incursion of the spindle. The nucleolus fragmented during prometaphase, and fragments were discarded with the interzonal region during telophase. Nucleoli appeared in daughter nuclei before chromatin became diffuse. Similarities in the mitotic apparatus of P. euglenae with that previously reported for Monoblepharella sp. support a phylogenetic affinity between members of the orders Chytridiales and Monoblepharidales. Key words: mitosis, Polyphagus euglenae, Chytridiales, centrosomes, phylogeny, ultrastructure.
8
Lloyd, C. W., and B. Wells. "Microtubules are at the tips of root hairs and form helical patterns corresponding to inner wall fibrils." Journal of Cell Science 75, no. 1 (1985): 225–38. http://dx.doi.org/10.1242/jcs.75.1.225.
Full textAbstract:
Root hairs have sometimes provided contradictory evidence for microtubule/microfibril parallelism. This tissue was re-examined using optimized conditions for the fixation, before immunofluorescence, of root hairs. In phosphate buffer, microtubules did not enter the apical tip of radish root hairs and were clearly fragmented. However, in an osmotically adjusted microtubule-stabilizing buffer, microtubules were observed within the apical dome and appeared unfragmented. Microtubules are not, therefore, absent from the region where new cell wall is presumed to be generated during tip growth. A spiralling of microtubules was seen at the apices of onion root hairs. Using shadow-cast preparations of macerated radish root hairs, it was confirmed that steeply helical microtubules matched the texture of the inner wall. In onion, the 45 degrees microtubular helices are accompanied by similarly wound inner wall fibrils. Results do not support the view that microtubules are not involved in the oriented deposition of fibrils in root hairs. Instead, they are interpreted in terms of a flexible helical cytoskeleton, which is capable of changing its pitch but is sensitive to fixation conditions.
9
Schroeder, C. C., A. K. Fok, and R. D. Allen. "Vesicle transport along microtubular ribbons and isolation of cytoplasmic dynein from Paramecium." Journal of Cell Biology 111, no. 6 (1990): 2553–62. http://dx.doi.org/10.1083/jcb.111.6.2553.
Full textAbstract:
Cytoplasmic microtubule-based motility in Paramecium was investigated using video-enhanced contrast microscopy, the quick-freeze, deep-etch technique, and biochemical isolations. Three distinct vesicle populations were found to be transported unidirectionally along the cytopharyngeal microtubular ribbons. This minus-end-directed movement exhibited unique in vivo features in that the vesicle transport was nonsaltatory, rapid, and predominantly along one side of the microtubular ribbons. To identify candidate motor proteins which may participate in vesicle transport, we prepared cytosolic extracts of Paramecium and used bovine brain microtubules as an affinity matrix. These preparations were found to contain a microtubule-stimulated ATPase which supported microtubule gliding in vitro. This protein was verified as a cytoplasmic dynein based upon its relative molecular mass, sedimentation coefficient of 16S, susceptibility to vanadate photocleavage, elevated CTPase/ATPase ratio, and its typical two-headed dynein morphology. This dynein was directly compared with the axonemal dyneins from Paramecium and found to differ by five criteria: morphology, sedimentation coefficient, CTPase/ATPase ratio, vanadate cleavage patterns, and polypeptide composition. The cytoplasmic dynein is therefore not an axonemal dynein precursor, but rather it represents a candidate for supporting the microtubule-based vesicle transport which proceeds along the microtubular ribbons.
10
Caplow, Michael, John Shanks, and Bruna Pegoraro Brylawski. "Concerning the location of the GTP hydrolysis site on microtubules." Canadian Journal of Biochemistry and Cell Biology 63, no. 6 (1985): 422–29. http://dx.doi.org/10.1139/o85-061.
Full textAbstract:
The kinetics for GTP hydrolysis associated with microtubule assembly with microtubular protein has been analyzed under reaction conditions where tubulin–GDP does not readily assemble into microtubules. The GTPase rate is only slightly faster during the time when net microtubule assembly occurs, as compared with steady state. The slightly slower steady-state GTPase rate apparently results from GDP product inhibition, since the progressive decrease in the rate can be quantitatively accounted for using the previously determined GTP dissociation constant and the Ki value for GDP. Since the GTPase rate is not a function of the rate for net microtubule assembly, it is concluded that GTP hydrolysis is not required for tubulin subunit incorporation into microtubules. The constancy of the rate indicates that the GTPase reaction occurs at a site, the concentration of which does not change during the assembly process. This result is consistent with a reaction scheme in which GTP hydrolysis occurs primarily at microtubule ends. We propose that hydrolysis occurs at microtubule ends, at the interface between a long core of tubulin–GDP subunits and a short cap of tubulin–GTP subunits.
Dissertations / Theses on the topic "Microtubuli"
1
Boekhoorn, Karin. "Microtubule associated proteins and plasticity in the developing and diseased brain." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2006. http://dare.uva.nl/document/89864.
Full text
2
Zanarella, Erica. "Functional analysis of EFHC1, a gene involved in Juvenile Myoclonic Epilepsy, in Drosophila." Doctoral thesis, Università degli studi di Padova, 2011. http://hdl.handle.net/11577/3421984.
Full textAbstract:
Mutations in the EFHC1 gene, encoding a novel microtubule binding protein, have been linked to juvenile myoclonic epilepsy. EFHC1 has been proposed to regulate cell division by controlling mitotic spindle organization and cerebral cortex lamination by modulating neuroblast migration. To understand EFHC1 function in vivo we generated knock-out Drosophila for the fly homolog Defhc1. We found that the NMJ synapse of Defhc1 mutants display an increased number of satellite boutons and increased spontaneous neurotransmitter release. Defhc1 binds to microtubules in vitro and overlaps in vivo with axonal and synaptic microtubules. Elimination of Defhc1 from synaptic terminals reduces the number of microtubule loops, whose presence correlates with halted bouton division, suggesting that Defhc1 is a negative regulator of bouton division. These results suggest that Defhc1 functions as an inhibitor of neurite growth by finely tuning the microtubule cytoskeleton dynamics and that EFHC1-dependent JME may result from augmented spontaneous neurotransmitter release due to overgrowth of neuronal processes.<br>Mutazioni nel gene EFHC1, che codifica per una proteina in grado di legarsi ai microtubuli, sono state correlate con l’insorgenza dell’Epilessia Mioclonica Giovanile (JME). Il gene EFHC1 è stato proposto come regolatore della divisione cellulare attraverso il controllo dell’organizzazione del fuso mitotico e come modulatore della migrazione dei neuroblasti nella corteccia cerebrale. Per comprendere in vivo la funzione del gene EFHC1 abbiamo generato il mutante knock-out per il gene omologo Defhc1 in Drosophila. Le sinapsi di giunzioni neuromuscolari (NMJ) di larve mutanti per Defhc1 mostrano un maggior numero di bottoni satellite e l’aumento del rilascio spontaneo di neurotrasmettitore. Esperimenti in vitro hanno dimostrato che la proteina Defhc1 si lega ai microtubuli e che in vivo colocalizza con i microtubuli sinaptici e assonali. In seguito all’eliminazione di Defhc1 dalle terminazioni sinaptiche è stata osservata una diminuzione del numero di loops formati dai microtubuli, la cui presenza è correlata con il blocco della divisione dei bottoni sinaptici, suggerendo che il gene Defhc1 possa essere un regolatore negativo della divisione dei bottoni sinaptici. Questi risultati suggeriscono che Defhc1, attraverso una fine regolazione della dinamicità dei microtubuli del citoscheletro, agisca da inibitore della crescita delle terminazioni sinaptiche tramite e che la JME dipendente da mutazione di EFHC1 potrebbe dipendere da un aumento del rilascio spontaneo di neurotrasmettitore conseguente all’eccessiva crescita sinaptica.
3
Schaedel, Laura. "Les propriétés mécaniques des microtubules." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAY010/document.
Full textAbstract:
Les microtubules-qui définissent la forme des axones, des cils et des flagelles, et qui servent de rails pour le transport intracellulaire-subissent de fortes contraintes exercées par les forces intracellulaires. La structure des microtubules et leur rigiditépeuvent en théorie être affectées par des contraintes physiques. Cependant, il reste à établir comment les microtubules tolèrent de telles forces et quelles sont les conséquences de ces forces sur la structure des microtubules. En utilisant un dispositif demicrofluidique, j’ai pu montrer que la rigidité des microtubules diminue progressivementà chaque cycle de courbure induit par des contraintes hydrodynamiques.Comme dans d'autres exemples de fatigue des matériaux, l'application de contraintes mécaniques sur des défauts pré-existants le long des microtubules est responsable de la génération de dommages plus étendus. Ce processus rend les microtubules moins rigides.J’ai pu aussi montrer que les microtubules endommagés peuvent se réparer en intégrant de nouveaux dimères de tubuline à leur surface et de récupérer ainsi leur rigidité initiale. Nos résultats démontrent que les microtubules sont des matériaux biologiquesayant des propriétés d’auto-réparation, et que la dynamique des microtubules ne se produit pas exclusivement à leurs extrémités. La mise en évidence de ces nouvelles propriétés permet de montrer comment les microtubules peuvent s’adapter à des contraintesmécaniques<br>Microtubules—which define the shape of axons, cilia and flagella, and provide tracks for intracellular transport—can be highly bent by intracellular forces, and microtubule structure and stiffness are thought to be affected by physical constraints. Yet how microtubules tolerate the vast forces exerted on them remains unknown. Here, by using a microfluidic device, we show that microtubule stiffness decreases incrementally with each cycle of bending and release. Similar to other cases of material fatigue, the concentration of mechanical stresses on pre-existing defects in the microtubule lattice is responsible for the generation of more extensive damage, which further decreases microtubule stiffness. Strikingly, damaged microtubules were able to incorporate new tubulin dimers into their lattice and recover their initial stiffness. Our findings demonstrate that microtubules are ductile materials with self-healing properties, that their dynamics does not exclusively occur at their ends, and that their lattice plasticity enables the microtubules’ adaptation to mechanical stresses
4
Barlukova, Ayuna. "Dynamic instability of microtubules and effect of microtubule targeting agents." Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0064.
Full textAbstract:
L'objectif de cette thèse est de proposer des modèles mathématiques permettant de décrire l'instabilité dynamique d'une population de microtubules (MTs) et l'effet de médicaments sur cette instabilité. L'instabilité dynamique des MTs joue un rôle extrêmement important dans les processus de la mitose et de la migration cellulaire et donc dans la progression tumorale. L'instabilité dynamique est un processus complexe qui implique différents états de la tubuline (polymérisée ou non-polymérisée, tubuline-GTP ou tubuline-GDP qui correspondent à deux états énergétiques différents des dimères) et qui résulte de processus chimiques (polymérisation, dépolymérisation, hydrolyse, recyclage, nucléation) liant ces différents états de la tubuline. Décrire cette complexité par le biais de modèles mathématiques permet alors de tester des hypothèses biologiques quant à l'impact de chacun de ces processus et l'action de molécules anti-MTs. De récents travaux suggèrent que le "vieillissement" des MTs impacte leur dynamique. Nous avons testé dans ce travail l'hypothèse que ce "vieillissement" accélère l'hydrolyse du GTP au sein de la tubuline. Nous avons construit de nouveaux modèles couplant deux équations de transport multi-D avec deux équations différentielles ordinaires impliquant des termes intégraux. Nous avons calibrer notre nouveau modèle à partir des données expérimentales; tester l'hypothèse biologique sur le mécanisme du processus de vieillissement; analyser la sensibilité du modèle par rapport aux paramètres décrivant les processus; tester différentes hypothèses quant l'effet des médicaments anti-MTs<br>The aim of this thesis is to design new mathematical models that are able to appropriately describe dynamic instability of a population of microtubules (MTs) and effect of drugs on MT dynamics. MT dynamic instability play an important role in the processes of mitosis and cell migration and, thus, in cancer progression. Dynamic instability is a complex process that involves different states of tubulin (polymerized or non-polymerized, GTP-tubulin or GDPtubulin that correspond to two different energetic states of tubulin dimers) that resulted from chemical processes (polymerization, depolymerization, hydrolysis, recycling, nucleation) linking these different states of tubulin. Description of this complexity by mathematical models enables one to test biological hypotheses concerning the impact of each process and action of drugs on microtubule dynamics. Recent observations show that MT dynamics depends on aging of MT. One of the aims of the work is to test the hypothesis that MT aging results from the acceleration of the GTP hydrolysis. We construct for that new models that couple two multidimensional transport equations with two ordinary differential equations involving integral terms. We have calibrated our models on the basis of experimental data; tested biological hypothesis on mechanism of aging process; performed a sensitivity analysis of the model with respect to parameters describing chemical processes; and tested hypotheses concerning actions of drugs
5
Faller, Elliott M. "Modulation of microtuble dynamics by the microtubule-associated protein MAP1a." Thesis, University of Ottawa (Canada), 2003. http://hdl.handle.net/10393/26371.
Full textAbstract:
Structural microtubule-associated proteins (MAPs) are capable of interacting with tubulin dimers to regulate the various dynamic stages of microtubules. MAP1a is predominant in the neuronal cell body, axons and dendrites of mature neurons. MAP1 a has been shown to bind microtubules to promote microtubule assembly in vitro. The MAP1a heavy chain molecule is associated with three light chains. The heavy chain, and all three light chains appear to associate with microtubules independent of each other. The purpose of this project was to measure the impact of myc-tagged MAP1 a fragments and myc-tagged light chains associated with MAP1a on microtubule dynamic phases in vivo. Cells from an epithelial kidney cell line (LLCPK1) that had been permanently transfected with human GFP-alpha tubulin were transiently transfected with myc tagged MAP1a heavy and light chain fragments. Cells expressing MAP1a and light chain fragments were used to make direct observations of microtubule dynamics in living cells using fluorescence microscopy. Microtubule ends were photographed at 4-second intervals using a digital camera over a 2-minute duration. All truncated MAP1 a heavy chain fragments that contained the microtubule-binding domain were shown to associate with microtubules. MAP1a fragments containing portions of the projection domain promoted growth and stability of microtubules. Truncated fragments containing different regions of the projection domain of MAP1a demonstrated variations in their impact on microtubule dynamic events by promoting growth or inhibition of shortening phases. Similar to full length MAP1a, LC3 also appeared to promote microtubule growth and stability. Results from the present study suggest that MAP1a and LC3 promote slow, stable growth of microtubules. This type of growth may be important in the maintenance and restructuring of adult neurons.
6
Paez, Claudia. "Etude fonctionnelle de la protéine associée aux microtubules XMAP215/ch-TOG." Phd thesis, Université de Grenoble, 2011. http://tel.archives-ouvertes.fr/tel-00597065.
Full textAbstract:
Résumé Les protéines XMAP215/ch-TOG appartiennent à une famille de protéines associées aux microtubules (MAPs), bien conservée tout au long de l'évolution, la famille XMAP215/Dis1. Cette famille joue un rôle dans la régulation du cytosquelette des microtubules (MT), en particulier pendant la division cellulaire. Chez l'humain, ch-TOG est la protéine surexprimée dans les tumeurs du colon et du foie, une protéine qui provient de cellules blastiques et de plusieurs formes de cancer. Certaines protéines XMAP215/ch-TOG ont été retrouvées dans différentes localisations cellulaires, toujours reliées aux MTs, donnant origine à une activité spécifique. Cependant, la localisation exacte de XMAP215/ch-TOG ainsi que son activité restait à être déterminées. Dans ce contexte scientifique, nous avons développé une série d'anticorps monoclonaux (mcAB) qui nous ont permis d'identifier deux populations différentes de la famille des protéines XMAP215/Dis1. Les images de microscopie confocale des cellules fixées ont montré une première localisation, la colocalisation bien connue XMAP215-microtubulaire (MT-XMAP215) qui s'observe pendant l'interphase et pendant la mitose (fuseau mitotique). Une deuxième localisation a été identifiée sur le bout plus des MTs, donnant XMAP215/ch-TOG comme faisant parti de la famille des protéines de bout plus (+TIPs). Cette deuxième colocalisation a été identifiée comme +TIP XMAP215/ch-TOG. La +TIP XMAP215 est la protéine la plus distale du bout des MTs. La hiérarchie a été établie en faisant la comparaison de la localisation de XMAP215/ch-TOG avec les protéines les plus connues du bout plus, telles qu'EB1, CLIP170 et p150Glued. Dans l'extrait mitotique de Xenopus laevis, les images obtenues in vivo par la microscopie de fluorescence par réflexion totale interne (TIRF) ont permis d'identifier une +TIP XMAP215 présente au bout des MTs qui polymérisent et dépolymérisent. Les images de microscopie cryo-électronique (Cryo-EM) ont montré une activité spécifique de la population +TIP XMAP215. Dans les solutions de tubuline pure, XMAP215 induit la formation de structures au bout des MTs, cette activité est compatible avec les mécanismes de croissance des MTs. Sur la base de nos résultats, nous proposons un modèle où XMAP215 se charge des dimères de tubuline en devenant une structure de type protofilament. Cette structure se lie au bout du MT en utilisant son domaine C-terminal, en rajoutant les dimères de tubuline et aussi certainement en participant à la fermeture de la structure microtubulaire même. La protéine interviendrait donc dans la dépolymérisation et aurait un rôle dans le mécanisme de dépolymérisation contrôlée. Une fois que l'addition de tubuline a eu lieu, la +TIP XMAP215 pourrait évoluer en MT-XMAP215, la forme la plus connue de la protéine qui a été associée au trafic des granules d'ARN. Mots cles : XMAP215, ch-TOG, microtubules, anticorps monoclonaux.
7
Rovini, Amandine. "De l'extrémité des microtubules aux mitochondries dans la neuroprotection mediee par l'olesoxime : vers une meilleure compréhension des mécanismes d'action des agents anti-microtubules." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM5512.
Full textAbstract:
Dans l’arsenal thérapeutique anticancéreux, les agents anti-microtubules (MTA) occupent une place essentielle dans le traitement de tumeurs solides et d’hémopathies malignes. Néanmoins, leur utilisation est limitée par l’induction d’une toxicité neurologique qui affecte la qualité de vie des patients et dont les mécanismes d’action demeurent peu compris. L’absence de solutions préventives ou curatives réellement efficaces, reflète la complexité des mécanismes d’action des MTA. Dans le cadre du projet « Mitotarget » (7ème PCRD) porté par le partenaire industriel Trophos, notre objectif était de préciser le mécanisme à l’origine de la neurotoxicité des MTA et d’évaluer le potentiel neuroprotecteur de l’olesoxime, composé ayant fait la preuve de son efficacité neuroprotectrice dans différents modèles de pathologies neurodégénératives. Nous montrons ici que les réseaux microtubulaire (dynamique des microtubules, localisation de la protéine EB1) et mitochondrial (motilité des mitochondries), cibles des MTA dans les cellules cancéreuses, sont aussi affectés dans les cellules de type neuronal. Leur préservation par l’olesoxime est nécessaire à l’établissement d’une neuroprotection. Ce travail met en évidence l’originalité du mécanisme d’action de l’olesoxime, premier neuroprotecteur capable d’agir tout à la fois sur les microtubules et les mitochondries, et souligne l’importance des liens étroits existant entre ces deux compartiments. Deux axes d’étude ont été initiés à la suite de ce projet afin de (i) déchiffrer les interconnexions microtubules-mitochondries dans la réponse des cellules cancéreuses aux MTA; (ii) préciser l’importance et la régulation post-traductionnelle de la protéine EB1 dans l’efficacité anti-migratoire des MTA. L’ensemble des données obtenues appelle à poursuivre la caractérisation des mécanismes de réponse aux agents anti-microtubules afin d’optimiser les stratégies thérapeutiques existantes<br>Nowadays, the so-called Microtubule Targeting Agents (MTAs) remain benchmark clinical treatments displaying high efficiency and are still widely used against a broad spectrum of tumors and hemopathies. The new compounds in clinical development and the discovery of their anti-angiogenic properties make them a family booming. However, MTAs treatment is limited by the occurrence of neurological toxicities that greatly impair patients quality of life and which mechanisms of action are still poorly understood. The current absence of really efficient curative of preventive strategies underline the complexity of MTA mechanisms of action. In the framework of the “MitoTarget” project from the 7th PCRD,lead by the industrial partner Trophos, we aimed to precise MTA neurotoxic mechanisms and to evaluate neuroprotective potential of olesoxime, a compound that already showed to be efficient in various models of neurodegenerative diseases. Our data show that microtubular (microtubule dynamics parameters, EB1 protein localization) and mitochondria (mitochondria) networks, MTA targeted compartments in cancer cells, are damaged in neuronal-like cells. Interestingly, olesoxime neuroprotective activity implies preservation of both microtubule and mitochondria from MTA-induced damages. This work highlights the original mechanism of action of olesoxime as the first neuroprotective agent able to act on both microtubule and mitochondria and underlines the strengthened link existing between these compartments. It thus gave rise to two side projects with the aim to (i) decipher microtubule-mitochondria interconnections in response to MTA treatment; (ii) precise the importance and regulation of EB1 in the anti-migratory efficacy of MTA by looking at EB1 post-translational modifications. Altogether, the data obtained incite to keep on characterizing mechanisms involved in response to MTA in order to optimize the existing therapeutic strategies
8
Rosas, Salvans Miquel 1987. "Understanding RanGTP dependent microtubule assembly : Idenification of DnaJB6 as a RanGTP regulated factor involved in microtubule organization during mitosis." Doctoral thesis, Universitat Pompeu Fabra, 2017. http://hdl.handle.net/10803/664169.
Full textAbstract:
Three microtubule (MT) assembly pathways participate in the assembly of the bipolar spindle: the centrosomal pathway, the augmin dependent amplification pathway and the RanGTP/chromosome dependent pathway. To form the spindle, all these MTs are organized by various classes of motor proteins into two interdigitating antiparallel arrays with their minus ends focused at the spindle poles. This focusing activity is provided by the minus-end directed motor proteins Dynein-Dynactin and HSET.
Spindle assembly can occur in the absence of centrosomes indicating that the RanGTP and augmin dependent pathways are sufficient. The RanGTP pathway can be studied in Xenopus laevis egg extracts. Addition of RanGTP to these extracts triggers a dynamic process of MT nucleation, stabilization and organization into asters and mini spindles. To obtain a global picture of the RanGTP pathway we used a proteomics approach and determined the interactome of the RanGTP-MTs that consists of 1263 proteins. Moreover we have analyzed the changes in this proteome to try to correlate them with the change in MT dynamic and organization observed upon different time of incubation of the egg extract with RanGTP. Although the composition of the proteome did not change, we found different patterns of recruitment for various protein groups. The proteome includes most of the known RanGTP regulated factors in mitosis and significantly overlaps with previously published spindle and taxol-MT proteomes. In addition it contains a large number of other proteins with described or undescribed functions in various cellular processes. We used this proteome to identify novel putative RanGTP regulated spindle assembly factors (SAFs). We identified DnaJB6 as a RanGTP regulated protein involved in spindle assembly. We found that it interacts with dynactin p150 in a RanGTP dependent manner specifically in M-phase. We show that DnaJB6 favors the stabilization of the Dynactin complex specifically in mitosis, regulating the activity of Dynein-Dynactin complex in bipolar spindle assembly and MT focusing at the spindle poles.<br>Tres vies de formació de microtúbuls (MT) participen en la formació del fus mitòtic: la centrosòmica, la via d’amplificació dependent d’Augmin i la via dependent de RanGTP o cromosòmica. Per formar el fus, tots aquests MTs són organitzats per diferents classes de proteïnes motores en dos feixos interconnectats de MTs antiparal·lels, amb els seus extrems negatius concentrats al pols del fus. Dynein-Dynactin i HSET s’encarreguen de concentrar els extrems negatius als pols.
El fus es pot formar també en absència de centrosomes, indicant que les vies de RanGTP i d’Augmin són suficients per formar-lo. La via de RanGTP es pot estudiar utilitzant extractes d’ous (EE) de Xenopus Laevis. L’addició de RanGTP activa un procés dinàmics de nucleació, estabilització i organització del MTs en asters i mini-fusos. Hem utilitzat la proteòmica com una aproximació per obtenir una visió global de la ruta de RanGTP i em descrit un interactoma dels RanGTP-MTs de 1263 proteïnes. A més, hem analitzat els canvis en aquest proteoma intentant correlacionar-los amb canvis en la dinàmica i l’organització observades al llarg de diferents temps d’incubació de l’EE amb RanGTP. Tot i que la composició del proteoma no varia, hem trobat diferents patrons de reclutament per varis grups de proteïnes. El proteoma inclou la majoria dels factors regulats per RanGTP en mitosis que es coneixen i te un elevat grau de solapament amb altres proteomes del fus i dels Taxol-MTs publicats prèviament. A més, conté un elevat nombre de proteïnes amb i sense roles descrits en varis processos cel·lulars. Hem utilitzat el proteoma dels RanGTP-MTs per identificar nous possibles factors regulats per Ran involucrats en la formació del fus. Hem identificat DnaJB6 com una proteïna regulada per Ran amb una funció en la formació del fus mitòtic. Hem descrit la interacció de DnaJB6 amb p150, dependent de RanGTP específicament en fase M. DnaJB6 afavoreix l’estabilització el complex Dynactin específicament en mitosis, regulant l’activitat de Dynein-Dynactin en l’establiment de la bipolaritat del fus mitòtic i la concentració dels extrems (-) dels MTs als pols del fus mitòtic.
9
A, S. Jijumon. "Systematic characterization of a large number of Microtubule-Associated Proteins using purification-free TIRF-reconstitution assays Purification of tubulin with controlled post-translational modifications by polymerization–depolymerization cycles Microtubule-Associated Proteins: Structuring the Cytoskeleton Purification of custom modified tubulin from cell lines and mouse brains by polymerization-depolymerization cycles." Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASL007.
Full textAbstract:
Le cytosquelette des microtubules (MTs) est constitué de filaments dynamiques impliqués dans une multitude de fonctions telles que la division cellulaire, le maintien de forme des cellules, les battements ciliaires ou encore la différenciation neuronale. Une régulation stricte des fonctions des MTs est donc d'une grande importance pour l'homéostasie cellulaire, et toute perturbation pourrait potentiellement conduire à des maladies comme le cancer, les ciliopathies ou la neurodégénérescence. Dans un contexte cellulaire, les propriétés des MTs peuvent être contrôlées par leurs interactions avec une grande variété de protéines associées (MT-associated proteins ; MAPs). Notre connaissance de ces interacteurs s'est continuellement enrichie au cours des dernières décennies, mais il n'existe à ce jour aucune étude systématique visant à décrire et à classer ces protéines en fonction de leurs mécanismes de liaison et de leurs effets structuraux sur les MTs. Dans mon projet de thèse, j’ai mis au point un essai permettant une analyse rapide et systématique à la base des lysats clarifiés de cellules humaines surexprimant une multitude des différents MAPs. Le comportement dynamique des MT en présence d'environ 50 MAPs différentes a été imagé à l'aide de la microscopie TIRF. Cela nous permet d'étudier le comportement des MAP dans une situation proche de leur environnement naturel, mais en éliminant la complexité de l'espace intracellulaire, telle que l'encombrement par des organelles et des filaments du cytosquelette à l'intérieur de l'espace intracellulaire confiné. En effet, la plupart des MAPs étaient bien solubles dans notre approche d'extraction, tandis que les approches de purification pour plusieurs d'entre elles ont conduit à leur précipitation, rendent les expériences de reconstitution in vitro classique impossible. Ma nouvelle approche m’a permis de définir plusieurs nouvelles protéines comme de véritables MAP. J’ai montré que des MAPs non-caractérisées auparavant ont des effets étonnamment différents sur la polymérisation et la structure des MTs, créant ainsi une variété de réseaux de MT distincts. J’ai également démontré que mon approche permet d'étudier les structures des MAPs associées aux MTs par cryo-microscopie électronique, ou d'étudier le dynamique des MTs porteuses de mutations trouvées dans les pathologies humaines. J’ai également démontré que mon approche permet à tester la sensibilité des MAPs aux modifications post-traductionnelles de la tubuline, ou d'étudier le rôle des MAPs dans les interactions entre l'actine et les MTs. Mon approche expérimentale permet donc de mieux comprendre comment les MAP et les MT contrôlent ensemble le fonctionnement du cytosquelette<br>Microtubules (MTs) are dynamic filaments involved in a plethora of functions such as cell division, cell shape, ciliary beating, neuronal differentiation. Strict regulation of MT functions is therefore of high importance for the cellular homeostasis, and any perturbations could potentially lead to diseases like cancer, ciliopathies and neurodegeneration. At the protein level, there are accumulating studies showing that MT properties can be controlled via interaction with a large variety of MT-associated proteins (MAPs). Our knowledge of MAPs has been enriched over time, but up to this date no systematic studies exist that aim to describe and categorize these proteins according to their binding mechanisms and structural effects on MTs. In my PhD project, I have developed an assay for rapid and systematic analysis of MAPs using cleared lysates of cultured human cells in which I overexpress a variety of different MAPs. The dynamic behaviour of growing MTs in the presence of those MAPs were imaged using TIRF microscopy. This allows me to study the behaviour of around 50 MAP candidates in a situation close to their natural environment, but eliminating complexity coming from different organelles and crammed cytoskeleton filaments inside the confined intracellular space. Indeed, most MAPs were nicely soluble in the extract approach, while purification attempts of several of them led to protein precipitation, thus making classical invitro reconstitution approaches impossible. This novel approach allowed me to compare many MAPs under similar experimental conditions, and helped to define several novel proteins as bona-fide MAPs. I demonstrate that previously uncharacterized MAPs have strikingly different effects on MT polymerization and MT structure, thus creating a variety of distinct MT arrays. I further extended this cell-free pipeline to study structures of MAPs bound to MTs by cryo-electron microscopy, or to study the MT interactions of MAPs carrying patient mutations. Finally, I demonstrated that my approach can be used to test the sensitivity of MAPs to tubulin PTMs, as well as to study the role of MAPs in actin-MT crosstalk. In the future, this novel approach will allow for a better mechanistic understanding of how MAPs and MTs together control cytoskeleton functions
10
Hunter, Andrew W. "Coupling of ATP hydrolysis to microtubule depolymerization by mitotic centromere-associated kinesin /." Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/10549.
Full textBooks on the topic "Microtubuli"
1
International Symposium on Microtubules and Microtubule Inhibitors (3rd 1985 Beerse). Microtubules and microtubule inhibitors, 1985: Proceedings on the 3rd International Symposium on Microtubules and Microtubule Inhibitors. Beerse, Belgium, 3-6 September, 1985. Edited by Brabander M. de, Mey J. de, Janssen Research Foundation, and Belgian Society for Cell Biology. Elsevier, 1985.
Find full text
2
International Symposium on Microtubules and Microtubule Inhibitors (3rd 1985 Beerse, Belgium). Microtubules and microtubule inhibitors, 1985: Proceedings of the 3rd International Symposium on Microtubules and Microtubule Inhibitors, Beerse, Belgium, 3-6 September, 1985. Edited by Brabander M. de, Mey J. de, Janssen Research Foundation, and Belgian Society for Cell Biology. Elsevier Science, 1985.
Find full text
3
Sutton, Michael Mark. The Influence of Microtubules and Microtubule-Based Structures on Osteoclast and CD4+ T Cell Function. [publisher not identified], 2022.
Find full text
4
Zhou, Jun, ed. Microtubule Protocols. Humana Press, 2007. http://dx.doi.org/10.1007/978-1-59745-442-1.
Full text
5
Straube, Anne, ed. Microtubule Dynamics. Humana Press, 2011. http://dx.doi.org/10.1007/978-1-61779-252-6.
Full text
8
Lüders, Jens, ed. The Microtubule Cytoskeleton. Springer Vienna, 2016. http://dx.doi.org/10.1007/978-3-7091-1903-7.
Full text
9
Nick, Peter, ed. Plant Microtubules. Springer Berlin Heidelberg, 2008. http://dx.doi.org/10.1007/978-3-540-77178-4.
Full text
10
Nick, Peter, ed. Plant Microtubules. Springer Berlin Heidelberg, 2000. http://dx.doi.org/10.1007/978-3-662-22300-0.
Full textBook chapters on the topic "Microtubuli"
1
Hamada, Takahiro, and Seiji Sonobe. "Isolation of Microtubules and Microtubule-Associated Proteins." In Isolation of Plant Organelles and Structures. Springer New York, 2016. http://dx.doi.org/10.1007/978-1-4939-6533-5_22.
Full text
2
Gooch, Jan W. "Microtubule." In Encyclopedic Dictionary of Polymers. Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4419-6247-8_14228.
Full text
3
Detrich, H. William. "Molecular Adaptation of Microtubules and Microtubule Motors from Antarctic Fish." In Fishes of Antarctica. Springer Milan, 1998. http://dx.doi.org/10.1007/978-88-470-2157-0_12.
Full text
4
Luo, Yanzhang, Shengqi Xiang, Alessandra Lucini Paioni, et al. "Solid-State NMR Spectroscopy for Studying Microtubules and Microtubule-Associated Proteins." In Methods in Molecular Biology. Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1406-8_10.
Full text
5
Blas-Rus, Noelia, Eugenio Bustos-Morán, Francisco Sánchez-Madrid, and Noa B. Martín-Cófreces. "Analysis of Microtubules and Microtubule-Organizing Center at the Immune Synapse." In The Immune Synapse. Springer New York, 2017. http://dx.doi.org/10.1007/978-1-4939-6881-7_3.
Full text
6
Grawenhoff, Julia, Sebastian Baumann, and Sebastian P. Maurer. "In Vitro Reconstitution of Kinesin-Based, Axonal mRNA Transport." In Methods in Molecular Biology. Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-1990-2_29.
Full textAbstract:
AbstractMotor protein-driven transport of mRNAs on microtubules and their local translation underlie important neuronal functions such as development, growth cone steering, and synaptic plasticity. While there is abundant data on how membrane-bound cargoes such as vesicles, endosomes, or mitochondria are coupled to motor proteins, surprisingly little is known on the direct interactions of RNA–protein complexes and kinesins or dynein. Provided the potential building blocks are identified, in vitro reconstitutions coupled to Total Internal Reflection Microscopy (TIRF-M) are a powerful and highly sensitive tool to understand how single molecules dynamically interact to assemble into functional complexes. Here we describe how we assemble TIRF-M imaging chambers suitable for the imaging of single protein–RNA complexes. We give advice on optimal sample preparation procedures and explain how a minimal axonal mRNA transport complex can be assembled in vitro. As these assays work at picomolar-range concentrations of proteins and RNAs, they allow the investigation of molecules that cannot be obtained at high concentrations, such as many large or disordered proteins. This now opens the possibility to study how RNA-binding proteins (RBPs), RNAs, and microtubule-associated proteins act together in real-time at single-molecule sensitivity to create cytoplasmic mRNA distributions.
7
Moritz, Michelle, Luke M. Rice, and David A. Agard. "Microtubule Nucleation." In Centrosomes in Development and Disease. Wiley-VCH Verlag GmbH & Co. KGaA, 2005. http://dx.doi.org/10.1002/3527603808.ch3.
Full text
8
Flyvbjerg, Henrik. "Microtubule Dynamics." In Physics of Biological Systems. Springer Berlin Heidelberg, 1997. http://dx.doi.org/10.1007/978-3-540-49733-2_10.
Full text
9
Osada, Yoshihito, Ryuzo Kawamura, and Ken-Ichi Sano. "Microtubule Gel." In Hydrogels of Cytoskeletal Proteins. Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-27377-8_4.
Full text
10
Hotta, Takashi, and Takashi Hashimoto. "Microtubule Nucleation." In Cell Biology. Springer New York, 2014. http://dx.doi.org/10.1007/978-1-4614-7881-2_16-1.
Full textConference papers on the topic "Microtubuli"
1
Sinha, S., and D. D. Wagner. "INTACT MICROTUBULES ARE NECESSARY FOR COMPLETE PROCESSING, STORAGE AND REGULATED SECRETION OF VON WILLEBRAND FACTOR BY ENDOTHELIAL CELLS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642914.
Full textAbstract:
The importance of intact microtubules in the processing, storage and regulated secretion of von Willebrand factor (vWf) from Weibel-Palade bodies in endothelial cells was investigated. Human umbilical vein endothelial cells treated for one hour with colchicine (10-6M) or nocodozole (10-6M) lost their organized microtubular network. Stimulation of these cells with secretagogues (A23187, thrombin) produced only 30% release of vWf in comparison to control cells containing intact microtubules. The nocodazole treatment was reversible. One hour incubation in the absence of the drug was sufficient for microtubules to reform and to restore the full capacity of the cells to release vWf.Long-term incubation (24 hours) of endothelial cells with microtubule destabilizing agents had a profound effect on vWf distribution. In control cells vWf was localized to organelles in the perinuclear region (i.e. endoplasmic reticulum and Golgi apparatus) and to Weibel-Palade bodies. In drug-treated cells vWf staining was dispersed throughout the cytoplasm and Weibel-Palade bodies were absent. The vWf synthesized in the absence of microtubules contained significantly less large multimers than that produced by control cells. This was not due to possible side effects of the drugs on the cells because the presence of lumicolchicine, an inactive analogue of colchicine, had no effect on vWf processing. Since Weibel-Palade bodies specifically contain the large multimers (Sporn et al, Cell 46:185-190, 1986), we hypothesize that the structural defect in vWf secreted by cells in the absence of microtubules is due to the lack of Weibel-Palade bodies in these cultures.In summary, the intact microtubular cytoskeleton in the endothelial cells in culture, appeared to be crucial for normal release of Weibel-Palade bodies after stimulation with secretagogues, for reformation of new Weibel-Palade bodies and for the efficient intracellular multimerization of vWf dimeric molecules.
2
Ghavanoo, E., F. Daneshmand, and M. Amabili. "Two-Dimensional Shell Vibration of Microtubule in Living Cell." In ASME 2010 3rd Joint US-European Fluids Engineering Summer Meeting collocated with 8th International Conference on Nanochannels, Microchannels, and Minichannels. ASMEDC, 2010. http://dx.doi.org/10.1115/fedsm-icnmm2010-30636.
Full textAbstract:
The mechanical behavior of a eukaryotic cell is mainly determined by its cytoskeleton. Microtubules immersed in cytosol are a central part of the cytoskeleton. Cytosol is the viscous fluid in living cells. The microtubules permanently oscillate in the cytosol. In this study, two-dimensional vibration of a single microtubule in living cell is investigated. The Donnell’s shell theory equations for orthotropic materials is used to model the microtubule whereas the motion of the cytosol is modeled as Stokes flow characterized by a small Reynolds number with no-slip condition at microtubule-cytosol interface. The stress field in the cytosol induced by vibrating microtubule is determined analytically and the coupled vibrations of the microtubule-cytoplasm system are investigated. A coupled polynomial eigenvalue problem is developed in the present study and the variations of eigenvalues of coupled system with cytosol dynamic viscosity, microtubule circumferential Young’s modulus and circumferential wave number are examined.
3
Kuznetsov, A. V., A. A. Avramenko, and D. G. Blinov. "Simulation of Traffic Jam Formation in Fast Axonal Transport." In ASME 2009 Heat Transfer Summer Conference collocated with the InterPACK09 and 3rd Energy Sustainability Conferences. ASMEDC, 2009. http://dx.doi.org/10.1115/ht2009-88345.
Full textAbstract:
Many neurodegenerative diseases, such as Alzheimer’s disease, are linked to swellings occurring in long arms of neurons. Many scientists believe that these swellings result from traffic jams caused by the failure of intracellular machinery responsible for fast axonal transport; such traffic jam can plug an axon and prevent the sufficient amount of organelles to be delivered toward the synapse of the axon. Mechanistic explanation of the formation of traffic jams in axons induced by overexpression of tau protein is based on the hypothesis that the traffic jam is caused not by the failure of molecular motors to transport organelles along individual microtubules but rather by the disruption of the microtubule system in an axon, by the formation of a swirl of disoriented microtubules at a certain location in the axon. This paper investigates whether a microtubule swirl itself, without introducing into the model microtubule discontinuities in the traffic jam region, is capable of capturing the traffic jam formation. The answer to this question can provide important insight into the mechanics of the formation of traffic jams in axons.
4
Aprodu, Iuliana, Alfonso Gautieri, Franco M. Montevecchi, Alberto Redaelli, and Monica Soncini. "What Molecular Dynamics Simulations Can Tell Us About Mechanical Properties of Kinesin and Its Interaction With Tubulin." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176316.
Full textAbstract:
Kinesin is a processive molecular motor found in various cells including neurons, that transports membrane-bound vesicles and organelles along the microtubule. Kinesin typically consists of three distinct domains: two large globular heads that attach to the microtubule, a central coiled region, and a light-chain that attaches to the cellular cargo. The metabolic energy that drives kinesins is provided in the form of ATP. The energy released by ATP hydrolysis is converted into direct movement after kinesin binds strongly to the microtubule. Two mechanisms were proposed to explain the movement of kinesin along microtubules: the “hand over hand” model in which the two heads alternate in the role of leading and the “inchworm” model in which one head always leads.
5
Mehrbod, Mehrdad, and Mohammad R. K. Mofrad. "On the Mechanics of Microtubule Filaments." In ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. http://dx.doi.org/10.1115/sbc2011-53896.
Full textAbstract:
Quantitative understanding of cell mechanics has challenged biological scientists during the past couple of decades. one of the promising attempts towards mechanical modeling of the cytoskeleton has been the “tensegrity” cytoskeletal model, which simplifies the complex network of cytoskeletal filaments as a structure merely composed of compression-bearing elements (hinge-ended struts) and tensile members (cables). This discrete model can interestingly explain many experimental observations in cell mechanics. However, evidence suggests that the simplicity of this model may undermine the accuracy of its predictions [1–2]. Continuum mechanics predicts that a free, simply-supported beam tends to buckle in the first mode of buckling and that is the case for an in vitro loading of a single microtubule. However, in vivo imaging of microtubules indicates that the buckling mostly occurs in higher modes. This buckling mode switch takes place mostly because of lateral support of microtubules via their connections to actin and intermediate filaments, which themselves are tensile members of the tensegrity cytoskeleton model. Since these loads are exerted throughout the microtubule length, they introduce a considerable amount of microtubule bending behavior. The objective of this paper is to explore the influence of this flexural behavior on the accuracy of the tensegrity model, given the model’s underlying assumption that “every single member bears solely either tensile or compressive behavior”.
6
Allen, Kathleen B., and Bradley E. Layton. "Mechanical Neural Growth Models." In ASME 2005 International Mechanical Engineering Congress and Exposition. ASMEDC, 2005. http://dx.doi.org/10.1115/imece2005-79445.
Full textAbstract:
Critical to being able to control the growth patterns of cell-based sensors is being able to understand how the cytoskeleton of the cell maintains its structure and integrity both under mechanical load and in a load-free environment. Our approach to a better understanding of cell growth is to use a computer simulation that incorporates the primary structures, microtubules, necessary for growth along with their observed behaviors and experimentally determined mechanical properties. Microtubules are the main compressive structural support elements for the axon of a neuron and are created via polymerization of α-β tubulin dimers. Our de novo simulation explores the mechanics of the forces between microtubules and the membrane. We hypothesize that axonal growth is most influenced by the location and direction of the force exerted by the microtubule on the membrane, and furthermore that the interplay of forces between microtubules and the inner surface of the cell membrane dictates the polar structure of axons. The simulation will be used to understand cytoskeletal mechanics for the purpose of engineering cells to be used as sensors.
7
Tan, X. Gary, Andrzej J. Przekwas, and Raj K. Gupta. "Macro-Micro Biomechanics Finite Element Modeling of Brain Injury Under Concussive Loadings." In ASME 2016 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2016. http://dx.doi.org/10.1115/imece2016-66218.
Full textAbstract:
Traumatic brain injury (TBI) occurs in many blunt, ballistic and blast impact events. During trauma axons in the white matter are especially vulnerable to injury due to the rapid mechanical loading of brain. The axonal pathology leads to cytoskeletal failure and disconnection. The microtubules are one of major structural components of the cytoskeleton filamentous network. By bridging the macroscopic forces acting on the whole brain with the cellular and subcellular failure, the macro-micro computational models in both time and space can help us better understand the complex biophysics and elucidate the injury mechanism of both severe and mild TBI (concussion). At the macroscopic scale we developed the high-fidelity anatomical human body finite element model (FEM) to predict intracranial pressures and strain and strain rate fields of brain in the blast event. The macro-scale models and the coupled blast and biomechanics approach were validated against test data of shock wave interacting with a surrogate head in the shock tube. The mechanical deformation of brain tissue was mapped to the white matter tracts to obtain local axonal strain and strain rate for the micromechanical models. We developed the micromechanical FEM of myelinated axons interconnected with the oligodendrocyte by the processes, utilizing a novel beam element free of rotational degrees of freedom (DOFs). The numerical results reveal the possible mechanism of impact-induced axon injury including demyelination, breakup of processes, and axonal varicosity. We also investigate the dynamic response of microtubules bundles under traumatic loading. Different from the commonly discrete bead-spring models, a network of microtubules cross-linked with microtubule-associated-protein (MAP) tau proteins was modeled by the nonlinear beam model. Tau protein is modeled by the rate-dependent bar element for its complicated material behavior. The model considers the rupture of microtubule and the failure of tau-tau interface and tau-microtubule interface. The simulation result of the combined effects of the failure of the cross-linked architecture and elongation and bending of the bundle are possibly correlated to the axonal undulations following traumatic loading observed in the experiments. The developed macro-micro biomechanics models can be used as a starting point for modeling the neurobiology effects and guide the design of novel injury protection strategies.
8
Oswald, Elizabeth S., Pen-hsiu Grace Chao, J. Chloe Bulinski, Gerard A. Ateshian, and Clark T. Hung. "The Role of Microtubule Organization in Chondrocyte Response to Osmotic Loading." In ASME 2007 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2007. http://dx.doi.org/10.1115/sbc2007-176634.
Full textAbstract:
The cytoskeleton, including actin filaments and microtubules, provides chondrocytes with structure, cytoplasmic organization, and intracellular transport. The cytoskeleton is known to be involved in cellular responses to physiologic mechanical and osmotic loading signals, including morphological changes and mechanostransduction [1, 2]. Here, we examine microtubule (MT) involvement in volume response of chondrocytes to osmotic loading, as well as organization of stable MT with hypoosmotic loading. We also explore the hypothesis that chondrocytes from different zones of cartilage possess cytoskeletons with different properties, which help explain variations in their volume response to osmotic loading in situ and in vitro [3].
9
Zhang, Biaobiao, W. Steve Shepard, and Candace L. Floyd. "Investigation of Stress Wave Propagation in Brain Tissues Through the Use of Finite Element Method." In ASME 2010 International Mechanical Engineering Congress and Exposition. ASMEDC, 2010. http://dx.doi.org/10.1115/imece2010-39994.
Full textAbstract:
Because axons serve as the conduit for signal transmission within the brain, research related to axon damage during brain injury has received much attention in recent years. Although myelinated axons appear as a uniform white matter, the complex structure of axons has not been thoroughly considered in the study of fundamental structural injury mechanisms. Most axons are surrounded by an insulating sheath of myelin. Furthermore, hollow tube-like microtubules provide a form of structural support as well as a means for transport within the axon. In this work, the effects of microtubule and its surrounding protein mediums inside the axon structure are considered in order to obtain a better understanding of wave propagation within the axon in an attempt to make progress in this area of brain injury modeling. By examining axial wave propagation using a simplified finite element model to represent microtubule and its surrounding proteins assembly, the impact caused by stress wave loads within the brain axon structure can be better understood. Through conducting a transient analysis as the wave propagates, some important characteristics relative to brain tissue injuries are studied.
10
Xu, Gang, Kate S. Wilson, Ruth J. Okamoto, Jin-Yu Shao, Susan K. Dutcher, and Philip V. Bayly. "The Apparent Flexural Rigidity of the Flagellar Axoneme Depends on Resistance to Inter-Doublet Sliding." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80220.
Full textAbstract:
Cilia are thin subcellular organelles that bend actively to propel fluid. The ciliary cytoskeleton (the axoneme) consists of nine outer microtubule doublets surrounding a central pair of singlet microtubules. Large bending deformations of the axoneme involve relative sliding of the outer doublets, driven by the motor protein dynein. Ciliary structure and function have been studied extensively, but details of the mechanics and coordination of the axoneme remain unclear. In particular, dynein activity must be switched on and off at specific times and locations to produce an oscillatory, propulsive beat. Leading hypotheses assert that mechanical feedback plays a role in the control of dynein activity, but these ideas remain speculative.
Reports on the topic "Microtubuli"
1
Bulinski, Chloe J. Novel Microtubule-Stabilizing Reagents. Defense Technical Information Center, 2005. http://dx.doi.org/10.21236/ada446411.
Full text
2
Atweh, George F. Microtubule-Targeting Therapy for Prostate Cancer. Defense Technical Information Center, 2007. http://dx.doi.org/10.21236/ada470022.
Full text
3
Cassimeris, Lynne. Microtubule Control of Metabolism in Prostate Cancer. Defense Technical Information Center, 2013. http://dx.doi.org/10.21236/ada597853.
Full text
4
Cassimeris, Lynne. Microtubule Control of Metabolism in Prostate Cancer. Defense Technical Information Center, 2013. http://dx.doi.org/10.21236/ada602436.
Full text
5
Hanash, Samir M. Regulation of Microtubule Stability in Breast Cancer. Defense Technical Information Center, 1999. http://dx.doi.org/10.21236/ada382840.
Full text
6
Frisch, Steven M. Are Microtubules Involved in Anoikis. Defense Technical Information Center, 2001. http://dx.doi.org/10.21236/ada397720.
Full text
7
Brumlik, Charles J., and Charles R. Martin. Template Synthesis of Metal Microtubules. Defense Technical Information Center, 1991. http://dx.doi.org/10.21236/ada232827.
Full text
8
Margerum, J. D. Applications Research Studies of Microtubules. Defense Technical Information Center, 1990. http://dx.doi.org/10.21236/ada225694.
Full text
9
Orr, George A. Taxol Resistance and Microtubule Dynamics in Breast Cancer. Defense Technical Information Center, 2002. http://dx.doi.org/10.21236/ada407181.
Full text
10
Ames, Bruce N. Zinc Deficiency and Microtubule Function in Prostate Cells. Defense Technical Information Center, 2006. http://dx.doi.org/10.21236/ada453370.
Full text