Academic literature on the topic 'Microtubules'
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Journal articles on the topic "Microtubules"
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Ray, S., E. Meyhöfer, R. A. Milligan, and J. Howard. "Kinesin follows the microtubule's protofilament axis." Journal of Cell Biology 121, no. 5 (June 1, 1993): 1083–93. http://dx.doi.org/10.1083/jcb.121.5.1083.
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We tested the hypothesis that kinesin moves parallel to the microtubule's protofilament axis. We polymerized microtubules with protofilaments that ran either parallel to the microtubule's long axis or that ran along shallow helical paths around the cylindrical surface of the microtubule. When gliding across a kinesin-coated surface, the former microtubules did not rotate. The latter microtubules, those with supertwisted protofilaments, did rotate; the pitch and handedness of the rotation accorded with the supertwist measured by electron cryo-microscopy. The results show that kinesin follows a path parallel to the protofilaments with high fidelity. This implies that the distance between consecutive kinesin-binding sites along the microtubule must be an integral multiple of 4.1 nm, the tubulin monomer spacing along the protofilament, or a multiple of 8.2 nm, the dimer spacing.
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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 (August 1, 1993): 873–81. http://dx.doi.org/10.1242/jcs.105.4.873.
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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.
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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 (April 1, 1985): 225–38. http://dx.doi.org/10.1242/jcs.75.1.225.
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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.
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Logan, Caitlin M., and A. Sue Menko. "Microtubules: Evolving roles and critical cellular interactions." Experimental Biology and Medicine 244, no. 15 (August 6, 2019): 1240–54. http://dx.doi.org/10.1177/1535370219867296.
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Microtubules are cytoskeletal elements known as drivers of directed cell migration, vesicle and organelle trafficking, and mitosis. In this review, we discuss new research in the lens that has shed light into further roles for stable microtubules in the process of development and morphogenesis. In the lens, as well as other systems, distinct roles for characteristically dynamic microtubules and stabilized populations are coming to light. Understanding the mechanisms of microtubule stabilization and the associated microtubule post-translational modifications is an evolving field of study. Appropriate cellular homeostasis relies on not only one cytoskeletal element, but also rather an interaction between cytoskeletal proteins as well as other cellular regulators. Microtubules are key integrators with actin and intermediate filaments, as well as cell–cell junctional proteins and other cellular regulators including myosin and RhoGTPases to maintain this balance. Impact statement The role of microtubules in cellular functioning is constantly expanding. In this review, we examine new and exciting fields of discovery for microtubule’s involvement in morphogenesis, highlight our evolving understanding of differential roles for stabilized versus dynamic subpopulations, and further understanding of microtubules as a cellular integrator.
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Gittes, F., B. Mickey, J. Nettleton, and J. Howard. "Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape." Journal of Cell Biology 120, no. 4 (February 15, 1993): 923–34. http://dx.doi.org/10.1083/jcb.120.4.923.
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Microtubules are long, proteinaceous filaments that perform structural functions in eukaryotic cells by defining cellular shape and serving as tracks for intracellular motor proteins. We report the first accurate measurements of the flexural rigidity of microtubules. By analyzing the thermally driven fluctuations in their shape, we estimated the mean flexural rigidity of taxol-stabilized microtubules to be 2.2 x 10(-23) Nm2 (with 6.4% uncertainty) for seven unlabeled microtubules and 2.1 x 10(-23) Nm2 (with 4.7% uncertainty) for eight rhodamine-labeled microtubules. These values are similar to earlier, less precise estimates of microtubule bending stiffness obtained by modeling flagellar motion. A similar analysis on seven rhodamine-phalloidin-labeled actin filaments gave a flexural rigidity of 7.3 x 10(-26) Nm2 (with 6% uncertainty), consistent with previously reported results. The flexural rigidity of these microtubules corresponds to a persistence length of 5,200 microns showing that a microtubule is rigid over cellular dimensions. By contrast, the persistence length of an actin filament is only approximately 17.7 microns, perhaps explaining why actin filaments within cells are usually cross-linked into bundles. The greater flexural rigidity of a microtubule compared to an actin filament mainly derives from the former's larger cross-section. If tubulin were homogeneous and isotropic, then the microtubule's Young's modulus would be approximately 1.2 GPa, similar to Plexiglas and rigid plastics. Microtubules are expected to be almost inextensible: the compliance of cells is due primarily to filament bending or sliding between filaments rather than the stretching of the filaments themselves.
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Sider, J. R., C. A. Mandato, K. L. Weber, A. J. Zandy, D. Beach, R. J. Finst, J. Skoble, and W. M. Bement. "Direct observation of microtubule-f-actin interaction in cell free lysates." Journal of Cell Science 112, no. 12 (June 15, 1999): 1947–56. http://dx.doi.org/10.1242/jcs.112.12.1947.
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Coordinated interplay of the microtubule and actin cytoskeletons has long been known to be crucial for many cellular processes including cell migration and cytokinesis. However, interactions between these two systems have been difficult to document by conventional approaches, for a variety of technical reasons. Here the distribution of f-actin and microtubules were analyzed in the absence of fixation using Xenopus egg extracts as an in vitro source of microtubules and f-actin, demembranated Xenopus sperm to nucleate microtubule asters, fluorescent phalloidin as a probe for f-actin, and fluorescent tubulin as a probe for microtubules. F-actin consistently colocalized in a lengthwise manner with microtubules of asters subjected to extensive washing in flow chambers. F-actin-microtubule association was heterogenous within a given aster, such that f-actin is most abundant toward the distal (plus) ends of microtubules, and microtubules heavily labeled with f-actin are found in close proximity to microtubules devoid of f-actin. However, this distribution changed over time, in that 5 minute asters had more f-actin in their interiors than did 15 minute asters. Microtubule association with f-actin was correlated with microtubule bending and kinking, while elimination of f-actin resulted in straighter microtubules, indicating that the in vitro interaction between f-actin and microtubules is functionally significant. F-actin was also found to associate in a lengthwise fashion with microtubules in asters centrifuged through 30% sucrose, and microtubules alone (i.e. microtubules not seeded from demembranated sperm) centrifuged through sucrose, indicating that the association cannot be explained by flow-induced trapping and alignment of f-actin by aster microtubules. Further, cosedimentation analysis revealed that microtubule-f-actin association could be reconstituted from microtubules assembled from purified brain tubulin and f-actin assembled from purified muscle actin in the presence, but not the absence, of Xenopus oocyte microtubule binding proteins. The results provide direct evidence for an association between microtubules and f-actin in vitro, indicate that this interaction is mediated by one or more microtubule binding proteins, and suggest that this interaction may be responsible for the mutual regulation of the microtubule and actomyosin cytoskeletons observed in vivo.
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Cassimeris, L., C. L. Rieder, G. Rupp, and E. D. Salmon. "Stability of microtubule attachment to metaphase kinetochores in PtK1 cells." Journal of Cell Science 96, no. 1 (May 1, 1990): 9–15. http://dx.doi.org/10.1242/jcs.96.1.9.
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Kinetochore microtubules are known to be differentially stable to a variety of microtubule depolymerization agents compared to the non-kinetochore polar microtubules, but the dynamics of microtubule attachment to the kinetochore is currently controversial. We have examined the stability of kinetochore microtubules in metaphase PtK1 spindles at 23 degrees C when microtubule assembly is abruptly blocked with the drug nocodazole. Metaphase cells were incubated in medium containing 34 microM nocodazole for various times before fixation and processing either for immunofluorescence light microscopy or serial-section electron microscopy. Microtubules not associated with kinetochore fibers disappeared completely in less than 1 min. Kinetochore fibers persisted and shortened, as the spindle poles moved close to the chromosomes over a 10–20 min interval. During this shortening process, the number of kinetochore microtubules decreased slowly. The mean number of kinetochore microtubules was 24 +/− 5 in control cells and zero in cells incubated with nocodazole for 20 min. The half-time of microtubule attachment to the kinetochore was approximately 7.5 min. These results show that when microtubule assembly is blocked, kinetochore microtubules shorten more slowly and persist about 10 times longer than the labile polar microtubules. If kinetochore microtubules shorten by tubulin dissociation at their plus-ends like the non-kinetochore polar microtubules, then the microtubule surface lattice must be able to translocate through the kinetochore attachment site without frequent detachment occurring.
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XuHan, X., and A. A. M. Van Lammeren. "Microtubular configurations during endosperm development in Phaseolus vulgaris." Canadian Journal of Botany 72, no. 10 (October 1, 1994): 1489–95. http://dx.doi.org/10.1139/b94-183.
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Microtubular cytoskeletons in nuclear, alveolar, and cellular endosperm of bean (Phaseolus vulgaris) were analyzed immunocytochemically and by electron microscopy to reveal their function during cellularization. Nuclear endosperm showed a fine network of microtubules between the wide-spaced nuclei observed towards the chalazal pole. Near the embryo, where nuclei were densely packed, bundles of microtubules radiated from nuclei. They were formed just before alveolus formation and functioned in spacing nuclei and in forming internuclear, phragmoplast-like structures that gave rise to nonmitosis-related cell plates. During alveolus formation cell plates extended and fused with other newly formed walls, thus forming the walls of alveoli. Growing wall edges of cell plates exhibited arrays of microtubules perpendicular to the plane of the wall, initially. When two growing walls were about to fuse, microtubules of both walls interacted, and because of the interaction of microtubules, the cell walls changed their position. When a growing wall was about to fuse with an already existing wall, such interactions between microtubules were not observed. It is therefore concluded that interactions of microtubules of fusing walls influence shape and position of walls. Thus microtubules control the dynamics of cell wall positioning and initial cell shaping. Key words: cell wall, cellularization, endosperm, microtubule, Phaseolus vulgaris.
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Infante, A. S., M. S. Stein, Y. Zhai, G. G. Borisy, and G. G. Gundersen. "Detyrosinated (Glu) microtubules are stabilized by an ATP-sensitive plus-end cap." Journal of Cell Science 113, no. 22 (November 15, 2000): 3907–19. http://dx.doi.org/10.1242/jcs.113.22.3907.
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Many cell types contain a subset of long-lived, ‘stable’ microtubules that differ from dynamic microtubules in that they are enriched in post-translationally detyrosinated tubulin (Glu-tubulin). Elevated Glu tubulin does not stabilize the microtubules and the mechanism for the stability of Glu microtubules is not known. We used detergent-extracted cell models to investigate the nature of Glu microtubule stability. In these cell models, Glu microtubules did not incorporate exogenously added tubulin subunits on their distal ends, while >70% of the bulk microtubules did. Ca(2+)-generated fragments of Glu microtubules incorporated tubulin, showing that Glu microtubule ends are capped. Consistent with this, Glu microtubules in cell models were resistant to dilution-induced breakdown. Known microtubule end-associated proteins (EB1, APC, p150(Glued) and vinculin focal adhesions) were not localized on Glu microtubule ends. ATP, but not nonhydrolyzable analogues, induced depolymerization of Glu microtubules in cell models. Timelapse and photobleaching studies showed that ATP triggered subunit loss from the plus end. ATP breakdown of Glu microtubules was inhibited by AMP-PNP and vanadate, but not by kinase or other inhibitors. Additional experiments showed that conventional kinesin or kif3 were not involved in Glu microtubule capping. We conclude that Glu microtubules are stabilized by a plus-end cap that includes an ATPase with properties similar to kinesins.
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Uyeda, T. Q., and M. Furuya. "Evidence for active interactions between microfilaments and microtubules in myxomycete flagellates." Journal of Cell Biology 108, no. 5 (May 1, 1989): 1727–35. http://dx.doi.org/10.1083/jcb.108.5.1727.
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We have previously observed the apparent displacement of microfilaments over microtubules in the backbone structure of permeabilized flagellates of Physarum polycephalum upon addition of ATP (Uyeda, T. Q. P., and M. Furuya. 1987. Protoplasma. 140:190-192). We now report that disrupting the microtubular cytoskeleton by treatment with 0.2 mM Ca2+ for 3-30 s inhibits the movement of the microfilaments induced by subsequent treatment with 1 mM Mg-ATP and 10 mM EGTA. Stabilization of microtubules by pretreatment with 50 microM taxol retarded both the disintegrative effect of Ca2+ on the microtubules and the inhibitory effect of Ca2+ on the subsequent, ATP-induced movement of the microfilaments. These results suggest that the movement of the microfilaments depends on the integrity of the microtubular cytoskeleton. EM observation showed that the backbone structure in control permeabilized flagellates consists of two arrays of microtubules closely aligned with bundles of microfilaments of uniform polarity. The microtubular arrays after ATP treatment were no longer associated with microfilaments, yet their alignment was not affected by the ATP treatment. These results imply that the ATP treatment induces reciprocal sliding between the microfilaments and the microtubules, rather than between the microfilaments themselves or between the microtubules themselves. While sliding was best stimulated by ATP, the movement was partially induced by GTP or ATP gamma S, but not by ADP or adenylyl-imidodiphosphate (AMP-PNP). AMP-PNP added in excess to ATP, 50 microM vanadate, or 2 mM erythro-9-[3-(2-hydroxynonyl)]adenine (EHNA) inhibited the sliding. Thus, the pharmacological characteristics of this motility were partly similar to, although not the same as, those of the known microtubule-dependent motilities.
Dissertations / Theses on the topic "Microtubules"
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Schaedel, Laura. "Les propriétés mécaniques des microtubules." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAY010/document.
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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 contraintesmécaniquesMicrotubules—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
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Barlukova, Ayuna. "Dynamic instability of microtubules and effect of microtubule targeting agents." Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0064.
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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-MTsThe 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
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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.
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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.
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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.
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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 existantesNowadays, 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
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Gaidar, Sergii, and Stefan Diez. "Dancing along microtubules." Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-182537.
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Peronne, Lauralie. "Caractérisation d'un nouveau composé pharmacologique qui potentialise la réponse des cellules au paclitaxel (Taxol®)." Thesis, Université Grenoble Alpes (ComUE), 2019. http://www.theses.fr/2019GREAV003.
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Les agents pharmacologiques ciblant la dynamique des microtubules (MTs) sont très utilisés en chimiothérapie des cancers agressifs. Le paclitaxel (PTX) est utilisé depuis des décennies et donne de bons résultats pour le traitement des tumeurs solides. Plusieurs inconvénients, notamment ses effets secondaires et la résistance de certains cancers limitent cependant l'efficacité de ce médicament. Dans le but d'identifier de nouveaux composés pharmacologiques qui sensibilisent les cellules au PTX, nous avons recherché, parmi une collection de 8000 molécules, celles capables de sensibiliser des cellules cancéreuses à une dose non toxique de PTX. Nous avons ainsi sélectionné un composé de la famille des carbazoles : Carba1. Dans les cellules, l’association carba1/PTX a un effet cytotoxique supérieur à la somme des effets de carba1 et de PTX, quand ces molécules sont appliquées séparément, indiquant un effet synergique. De plus, des analyses approfondies de différents phénotypes ont permis de montrer que l'administration de carba1 avait pour conséquence d'amplifier des effets du PTX.À fortes doses, carba1 entraine un blocage des cellules en prométaphase mais n’altère pas le réseau microtubulaire, ni en interphase ni en mitose. En revanche, in vitro, carba1 cible la tubuline en se fixant sur le site colchicine, provoquant un retard et une diminution de la polymérisation des MTs. En plus de la tubuline, des études génétiques réalisées sur la levure suggèrent que carba1 a d'autres cibles dont CENP-E, kinésine essentielle à l’alignement des chromosomes au cours de la mitose.Des études menées sur un modèle de cancer mammaire murin agressif (allogreffes) ont révélé que carba1 seul et carba1/PTX ne présentaient aucune toxicité. De plus, les effets anti-tumoraux et anti-métastatiques de la combinaison carba1/PTX sur ces modèles se sont montrés encourageants, bien que des mises au point, notamment sur la posologie sont encore à prévoir. Carba1 est une molécule nouvelle, avec des applications jusque-là inconnues. C’est pourquoi une déclaration d’invention, en vue d'un dépôt de brevet, a été soumise au CNRSMicrotubules (MTs) targeting agents are a powerful weapon in the war against aggressive cancers. Paclitaxel (PTX) has been used successfully for the treatment of solid tumors for decades. Several features, including side-effects and resistance of some cancers make this drug not always effective. With the aim to identify new chemical compounds that sensitize cells to paclitaxel we screened a library of 8,000 compounds, to select those not toxic for cell cultures when applied alone, that become toxic when applied in combination with a non-toxic dose of paclitaxel. This lead to the selection of a carbazole derivative: carba1. In cells, the carba1/PTX combination has a greater cytotoxic effect than the addition of the effects of each drug assayed separately, indicating a synergistic effect. In addition, in-depth phenotypic analyzes indicate that the administration of carba1 amplify the effects of PTX.High doses of carba1 induce a cell blockade in prometaphase, but do not alter the MT network in interphase or mitosis. In contrast, in vitro, carba1 targets the tubulin colchicine binding site, causing a delay and a decrease in MT polymerization. Genetic studies conducted on yeast indicated other potential additional targets including CENP-E, an essential kinesin for chromosome alignment during mitosis.Studies conducted on a preclinical mouse model of aggressive breast cancer (orthotopic grafts) revealed that carba1 alone and carba1/PTX showed no toxicity. In addition, the anti-tumor and anti-metastatic effects of the carba1/PTX combination on these models have been encouraging, but an optimization of the posology is still needed. Carba1 is a new molecule, with previously unknown applications. This is why a declaration of invention, with a view to filing a patent, has been submitted to the CNRS
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Le, Grand Marion. "La protéine Akt, lien entre mitochondries et microtubules dans le mécanisme d'action des agents anti-microtubules ou quand les MTA s'invitent dans de nouvelles stratégies thérapeutiques." Thesis, Aix-Marseille, 2015. http://www.theses.fr/2015AIXM5017/document.
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De nos jours, les agents anti-microtubules (MTA) sont administrés dans de nombreuses pathologiques cancéreuses reflétant ainsi leur grande efficacité anti-tumorale. Cependant, leur utilisation se voit limitée pour deux raisons : (i) l’apparition d’effets indésirables et, (ii) l’émergence de cellules tumorales résistantes. Pour palier ces problèmes, les MTA font l’objet de nombreux travaux de recherche faisant ainsi de ces composés des médicaments toujours dans l’ère du temps. L’objectif principal des travaux présentés dans ce manuscrit repose sur l’étude du mécanisme d’action des MTA afin d’optimiser, par la suite, leur administration. Dans une première partie s’inscrivant dans le domaine de la recherche fondamentale, nous avons caractérisé les mécanismes moléculaires à l’origine de l’efficacité anticancéreuse de ces agents. En effet, nous avons mis en lumière l’existence d’un pont signalétique entre les mitochondries et les microtubules avec un rôle crucial de la voie de signalisation Akt/GSK3β plaçant ainsi, de façon inattendue, la kinase Akt au cœur de l’efficacité des MTA. Ces résultats fournissant un rationnel mécanistique aux stratégies thérapeutiques associant les MTA aux thérapies ciblées anti-Akt, nous avons alors mené une étude oncopharmacologique démontrant que l’association MTA/anti-Akt est fortement synergique in vitro et in vivo.Mieux comprendre le mécanisme d’action des MTA, afin de proposer de nouvelles stratégies thérapeutiques aux cliniciens était l’objectif principal de cette thèse. Les résultats obtenus ici ouvrent ainsi la voie de l’association de ces agents avec les thérapies ciblées anti-Akt nouvelle générationMicrotubule-Targeting Agents (MTA) are a broad group of anticancer drugs that are currently administered in a lot of cancers. Nevertheless, they can cause undesired side effects and can lose their effectiveness as a result of resistance development. The main objective of my PhD work was to characterize the MTA’s mechanism of action in order to optimize their administration in the future. In the first part, we demonstrated the important role of the kinase Akt in MTA effects. In the second part, we evaluated the interest to combine MTA with anti-Akt drugs. We observed that MTA efficacy is highly important with Akt targeting drugs, particularly in lung adenocarcinoma. These promising results will need further explorations in order to develop more convenient cancer therapy strategies
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Gallaud, Emmanuel. "Caractérisation du rôle d'Ensconsine / MAP7 dans la dynamique des microtubules et des centrosomes." Thesis, Rennes 1, 2014. http://www.theses.fr/2014REN1S004/document.
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La mitose est une étape essentielle du cycle cellulaire à l’issue de laquelle le génome répliqué de la cellule mère est ségrégé de façon équitable entre les deux cellules filles. Pour cela, la cellule assemble une structure hautement dynamique et composée de microtubules, appelée le fuseau mitotique. En plus d’assurer la bonne ségrégation des chromosomes, le fuseau mitotique détermine l’axe de division, un phénomène particulièrement important pour la division asymétrique où des déterminants d’identité cellulaire doivent être distribués de façon inéquitable entre les deux cellules filles. L’assemblage et la dynamique de ce fuseau sont finement régulés par de nombreuses protéines qui sont associées aux microtubules. Au cour de ma thèse, nous avons identifié 855 protéines constituant l’interactome des microtubules de l’embryon de Drosophile par spectrométrie de masse puis criblé par ARNi 96 gènes peu caractérisés pour un rôle en mitose dans le système nerveux central larvaire. Par cette approche, nous avons identifié 18 candidats sur la base de leur interaction aux microtubules et de leur phénotype mitotique, dont Ensconsine/MAP7. Nous avons montré qu’Ensconsine est capable de s’associer aux microtubules du fuseau et favorise leur polymérisation. De plus, les neuroblastes des larves mutantes présentent des fuseaux raccourcis et une durée de mitose prolongée. Ce délai en mitose est dû à une activation prolongée du point de contrôle du fuseau mitotique qui est essentiel pour une ségrégation correcte des chromosomes en l’absence d’Ensconsine. D’autres part, en association avec la Kinésine-1, son partenaire fonctionnel en interphase, nous avons montré qu’Ensconsine est également impliquée dans la séparation des centrosomes au cours de l’interphase. Ceci entraine une distribution aléatoire des centrosomes pères et fils dans cellules filles. Grâce à cette étude, nous avons révélé deux nouvelles fonctions pour Ensconsine : elle favorise la polymérisation des microtubules et participe donc à l’assemblage du fuseau mitotique et est impliquée, avec la Kinésine-1 dans la dynamique des centrosomesMitosis is a key step of the cell cycle that allows the mother cell to segregate its replicated genome equally into the two daughter cells. To do so, the cell assembles a highly dynamic structure composed of microtubules called the mitotic spindle. Additionally to its role in the faithful segregation of chromosomes, the mitotic spindle defines the axis of cell division. This phenomenon is particularly important for the asymmetric cell division in which cell fate determinants have to be unequally distributed between the two daughter cells. Spindle assembly and dynamics are subtly regulated by numerous microtubules-associated proteins. During my PhD, we identified using mass spectrometry, 855 proteins establishing the Drosophila embryo microtubule interactome. An RNAi screen was performed in the larval central nervous system for 96 poorly described genes, in order to identify new mitotic regulators. Based on microtubule interaction and mitotic phenotype, among 18 candidates we focused on Ensconsin/MAP7. We have shown that Ensconsin is associated with spindle microtubules and promotes their polymerization. Neuroblasts from mutant larvae display shorter spindles and a longer mitosis duration. This mitotic delay is a consequence of an extended activation of the spindle assembly checkpoint, which is essential for the proper chromosome segregation in the absence of Ensconsin. This study also showed that, in association with its interphase partner Kinesin-1, Ensconsin is involved in centrosome separation during interphase. As a result, mother and daughter centrosomes are randomly distributed between the daughter cells. In conclusion, we highlighted two news functions of Ensconsin : first, this protein promotes microtubule polymerization and is involved in spindle assembly ; second, Ensconsin and its partner Kinesin-1 regulate centrosome dynamics
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METOZ, FREDERIC. "Reconstruction tridimensionnelle de microtubules." Université Joseph Fourier (Grenoble), 1996. http://www.theses.fr/1996GRE10118.
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Les microtubules sont des elements fondamentaux du cytosquelette de la quasi-totalite des cellules eucaryotes. Ils forment de longues structures filamenteuses et participent a des structures complexes de fonctions diverses, telles le mouvement ciliaire, la division cellulaire et le transport d'organelles. Cette derniere fonction fait intervenir les proteines motrices dont la queue se fixe aux organelles, et la tete court le long des microtubules. L'elucidation d'un tel mecanisme de transport necessite l'etude structurale des microtubules, associes ou non a la proteine moteur. L'heterodimere de tubuline polymerise tete-beche en longs filaments ou protofilaments. Ces derniers s'assemblent pour former la paroi du microtubule. Selon la position relative des protofilaments adjacents, deux reseaux peuvent decrire un reseau de surface helicoidal. Mais certaines configurations sont incompatibles avec ce modele: une discontinuite vient rompre la symetrie helicoidale. Cette discontinuite qui etale l'information dans l'espace reciproque rend difficile l'utilisation des logiciels de reconstruction helicoidaux. C'est pourquoi la technique de reconstruction par tomographie a ete utilisee pour ces elements: les calculs se font principalement dans l'espace direct. Chacune des techniques a d'abord ete testee sur des images simulees, puis appliquee aux microtubules seuls et aux complexes microtubules-proteine moteur
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Arslan, Mélis. "Micromechanical modeling of microtubules." Paris, ENMP, 2010. http://www.theses.fr/2010ENMP1684.
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Les microtubules sont des composants structuraux de cellules et gouvernent des fonctions cellulaires essentielles telles que les mitoses et le transport des vésicules. Ils sont composés de deux sous-unités non identiques (tubulines α et β), formant un dimère, et sont arrangés de sorte à former une structure tubulaire de 20nm de diamètre. Généralement, ils sont constitués de 13 ou 14 protofilaments arrangés en spirale. Les liaisons longitudinales entre dimères sont plus rigides et fortes que les liaisons latérales. Aussi, les microtubules sont des structures fortement anisotropes. Dans ces travaux de thèse, nous avons pour but de définir l'ensemble des coefficients élastique qui permet de reproduire leur comportement atomistique ainsi que de rendre compte de leur réponse mécanique selon des chemins de chargement variés. En négligeant la discontinuité hélicoïdale souvent observée, un microtubule est représenté par une structure triangulaire de dimères à partir desquels un volume élémentaire représentatif est défini. Un potentiel harmonique est utilisé pour décrire les interactions entre dimères voisins. A partir de l'estimation des constantes élastiques et de l'utilisation de la méthode proposée par Arslan et Boyce (2006) -alors pour analyser le comportement mécanique d'un réseau triangulaire de spectrines composant les membranes des globules rouges-, un modèle continu de comportement mécanique est présenté pour reproduire le comportement des parois des microtubules. Un modèle numérique éléments finis est ensuite créé pour modéliser le comportement d'un microtubule dans sa globalité. Des éléments coques sont utilisés pour reproduire les fines parois des microtubules. Les propriétés du modèle éléments finis sont ajustées à partir des résultats du modèle présenté ainsi qu'aux données expérimentales provenant de la littérature. La rigidité de flexion calculée au cours de simulation des tests de flexion 3 points est en accord avec les valeurs de la littérature. Ces tests révèlent les mécanismes de déformation en fonction de la longueur utile du tube utilisé: Flexion et cisaillement locaux de la paroi gouvernent la déformation pour de "petits" tubes. Pour des longueurs "moyennes" le cisaillement et la flexion du tube prédominent. Enfin, dans le cas de tubes "longs", la déformation est uniquement associée aux effets de flexion. Ces résultats témoignent de l'influence de l'anisotropie du tube sur la réponse observée selon différents mode de sollicitation. Ils permettent également d'expliquer l'évolution de la rigidité de flexion avec la longueur utile du tube, comme reportée dans la littérature. Enfin, des micrographes montrent la propension des extrémités des microtubules à diverger radialement -"à boucler"-. Une telle géométrie est causée par des instabilités propres aux microtubules et implique un état précontraint. Un «modèle d'interactions» est alors proposé de manière à considérer un état précontraint et ainsi reproduire la cinétique des instabilités des microtubules au cours de la polymérisation/dépolymérisationMicrotubules serve as one of the structural components of the cell and take place in some of the important cellular functions such as mitosis and vesicular transport. Microtubules comprise of tubulin subunits tubulin dimers arranged in a cylindrical beta and formed by alpha hollow tube structure with a diameter of 20nm. They are typically comprised of 13 or 14 protofilaments arranged in spiral configurations. The longitudinal bonds between the tubulin dimers are much stiffer and stronger than the lateral bonds. This implies the anisotropic structure and properties of the microtubule. In this work, the aim is to define a complete set of elastic properties that capture the atomistic behavior and track the deformation of the microtubules under different loading conditions. A seamless microtubule wall is represented as a two dimensional triangulated lattice of dimers from which a representative volume element can be defined. A harmonic potential is adapted for the dimer–dimer interactions. Estimating the lattice elastic constants and following the methodology from the analysis of the mechanical behavior of triangulated spectrin network of the red blood cell membrane (Arslan and Boyce, 2006); a general continuum level constitutive model of the mechanical behavior of the microtubule lattice wall is developed. The model together with the experimental data given in the literature provides an insight to defining the parameters required for the discrete numerical model created in finite element analysis medium. The three point bending simulations for a microtubule modeled using shell elements, give tube bending stiffness values that are in accordance with the experimental bending stiffness values. The micrographs also show that shrinking ends of microtubules (due to microtubule instabilities) curl out. This implies the existence of prestress. A “connector model” is proposed to include the effect of the prestress and to capture the dynamic instabilities of microtubules
Books on the topic "Microtubules"
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S, Hyams Jeremy, and Lloyd Clive W, eds. Microtubules. New York: Wiley-Liss, 1994.
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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. Amsterdam: Elsevier Science, 1985.
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Nick, Peter, ed. Plant Microtubules. Berlin, Heidelberg: Springer Berlin Heidelberg, 2008. http://dx.doi.org/10.1007/978-3-540-77178-4.
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Nick, Peter, ed. Plant Microtubules. Berlin, Heidelberg: Springer Berlin Heidelberg, 2000. http://dx.doi.org/10.1007/978-3-662-22300-0.
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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. Oxford: Elsevier, 1985.
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service), ScienceDirect (Online, ed. Microtubules: In vivo. Amsterdam: Elsevier/Academic Press, 2010.
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service), ScienceDirect (Online, ed. Microtubules, in vitro. Amsterdam: Elsevier/Academic Press, 2010.
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Lutz, Regina Anna. Regulation of Polarity by Microtubules. [New York, N.Y.?]: [publisher not identified], 2015.
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Sutton, Michael Mark. The Influence of Microtubules and Microtubule-Based Structures on Osteoclast and CD4+ T Cell Function. [New York, N.Y.?]: [publisher not identified], 2022.
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Wróbel, Zygmunt. Automatyczne metody analizy orientacji mikrotubul. Katowice: Wydawn. Uniwersytetu Śląskiego, 2007.
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Wade, Richard H. "Microtubules." In Methods in Molecular Medicine™, 1–16. Totowa, NJ: Humana Press, 2007. http://dx.doi.org/10.1007/978-1-59745-442-1_1.
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Wasteneys, Geoffrey O., and Bettina Lechner. "Microtubules." In Cellular Domains, 229–43. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2011. http://dx.doi.org/10.1002/9781118015759.ch14.
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Sabnis, D. D. "Microtubules." In Cell Components, 375–94. Berlin, Heidelberg: Springer Berlin Heidelberg, 1985. http://dx.doi.org/10.1007/978-3-642-82587-3_18.
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Visintin, Rosella. "Microtubules." In Encyclopedia of Systems Biology, 1358. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4419-9863-7_1432.
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Schliwa, Manfred. "Microtubules." In The Cytoskeleton, 47–82. Vienna: Springer Vienna, 1986. http://dx.doi.org/10.1007/978-3-7091-7667-2_3.
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Gooch, Jan W. "Microtubules." In Encyclopedic Dictionary of Polymers, 907. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4419-6247-8_14230.
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Dráber, Pavel, and Eduarda Dráberová. "Microtubules." In Cytoskeleton and Human Disease, 29–53. Totowa, NJ: Humana Press, 2012. http://dx.doi.org/10.1007/978-1-61779-788-0_2.
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Gupta, G. S. "Microtubules." In Proteomics of Spermatogenesis, 167–90. Boston, MA: Springer US, 2005. http://dx.doi.org/10.1007/0-387-27655-6_8.
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Iwanski, Malina K., Eugene A. Katrukha, and Lukas C. Kapitein. "Lattice Light-Sheet Motor-PAINT: A Method to Map the Orientations of Microtubules in Complex Three-Dimensional Arrays." In Single Molecule Analysis, 151–74. New York, NY: Springer US, 2023. http://dx.doi.org/10.1007/978-1-0716-3377-9_8.
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AbstractMicrotubules play an essential role in many cellular functions, in part by serving as tracks for intracellular transport by kinesin and dynein. The ability of microtubules to fulfill this role fundamentally depends on the fact that they are polar, with motors moving along them toward either their plus or minus end. Given that the microtubule cytoskeleton adopts a variety of specialized architectures in different cell types, it is important to map precisely how microtubules are oriented and organized in these cells. To this end, motor-PAINT has been developed, but in its current implementation, it relies on total internal reflection fluorescence (TIRF) microscopy and is thus restricted to imaging microtubules in a thin section of the cell immediately adjacent to the coverslip. Here, we report a variant of motor-PAINT that uses lattice light-sheet microscopy to overcome this, allowing for the mapping of microtubule organization and orientation in three-dimensional samples. We describe the necessary steps to purify, label, use, and image kinesin motors for motor-PAINT and outline the analysis pipeline used to visualize the resulting data. The method described here can be used in the future to study the microtubule cytoskeleton in (thick) polarized cells such as intestinal epithelial cells.
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Heinlein, Manfred. "Microtubules and Viral Movement." In Plant Microtubules, 141–73. Berlin, Heidelberg: Springer Berlin Heidelberg, 2008. http://dx.doi.org/10.1007/7089_2007_147.
Full textConference papers on the topic "Microtubules"
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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”.
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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.
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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.
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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.
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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.
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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.
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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].
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Huang, Y., M. Uppalapati, W. Hancock, and T. Jackson. "Movement Control of Confined Microtubules." In 2006 64th Device Research Conference. IEEE, 2006. http://dx.doi.org/10.1109/drc.2006.305158.
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Mikheenko, Pavlo. "Ideal Diamagnetism in Brain Microtubules." In 2022 IEEE 12th International Conference Nanomaterials: Applications & Properties (NAP). IEEE, 2022. http://dx.doi.org/10.1109/nap55339.2022.9934729.
Full textReports on the topic "Microtubules"
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Frisch, Steven M. Are Microtubules Involved in Anoikis. Fort Belvoir, VA: Defense Technical Information Center, August 2001. http://dx.doi.org/10.21236/ada397720.
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Brumlik, Charles J., and Charles R. Martin. Template Synthesis of Metal Microtubules. Fort Belvoir, VA: Defense Technical Information Center, March 1991. http://dx.doi.org/10.21236/ada232827.
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Margerum, J. D. Applications Research Studies of Microtubules. Fort Belvoir, VA: Defense Technical Information Center, August 1990. http://dx.doi.org/10.21236/ada225694.
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Fisher, D. D., and R. J. Cyr. Calmodulin immunolocalization to cortical microtubules is calcium independent. Office of Scientific and Technical Information (OSTI), December 1992. http://dx.doi.org/10.2172/10156994.
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Fisher, D. D., and R. J. Cyr. Calmodulin immunolocalization to cortical microtubules is calcium independent. Office of Scientific and Technical Information (OSTI), January 1992. http://dx.doi.org/10.2172/6434308.
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Cyr, R. Role of Ca[sup ++]/calmodulin in the regulation of microtubules in higher plants. Office of Scientific and Technical Information (OSTI), January 1991. http://dx.doi.org/10.2172/7137008.
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Cyr, R. Role of Ca[sup ++]/calmodulin in the regulation of microtubules in higher plants. Office of Scientific and Technical Information (OSTI), January 1992. http://dx.doi.org/10.2172/6528240.
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Cyr, R. Role of Ca{sup ++}/calmodulin in the regulation of microtubules in higher plants. Progress report, FY91. Office of Scientific and Technical Information (OSTI), December 1991. http://dx.doi.org/10.2172/10109506.
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Cyr, R. Role of Ca{sup ++}/calmodulin in the regulation of microtubules in higher plants. Progress report, FY 1992. Office of Scientific and Technical Information (OSTI), December 1992. http://dx.doi.org/10.2172/10159592.
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Bulinski, Chloe J. Novel Microtubule-Stabilizing Reagents. Fort Belvoir, VA: Defense Technical Information Center, September 2005. http://dx.doi.org/10.21236/ada446411.
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