Dynamic instability of microtubule growth

Mitchison, Tim; Kirschner, Marc W.

doi:10.1038/312237a0

Cited by 3,055 publications

(2,469 citation statements)

References 16 publications

Supporting

Mentioning

2,391

Contrasting

Unclassified

Order By: Relevance

“…Consistent with this rationale, kinesin-14 type complexes were previously proposed to operate within multi-motor ensembles to collectively organize microtubule networks in vivo 59,60 . This arrangement would also be consistent with the fact that microtubule minus ends are relatively static, whereas plus ends are mobile and often engage in so-called dynamic instability, which is defined by cycles of microtubule growth and shortening 61 .…”

Section: Discussionsupporting

confidence: 70%

Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process

et al. 2015

View full text Add to dashboard Cite

DNA double-strand breaks (DSBs) are often targeted to nuclear pore complexes (NPCs) for repair. How targeting is achieved and the DNA repair pathways involved in this process remain unclear. Here, we show that the kinesin-14 motor protein complex (Cik1-Kar3) cooperates with chromatin remodellers to mediate interactions between subtelomeric DSBs and the Nup84 nuclear pore complex to ensure cell survival via break-induced replication (BIR), an error-prone DNA repair process. Insertion of a DNA zip code near the subtelomeric DSB site artificially targets it to NPCs hyperactivating this repair mechanism. Kinesin-14 and Nup84 mediate BIR-dependent repair at non-telomeric DSBs whereas perinuclear telomere tethers are only required for telomeric BIR. Furthermore, kinesin-14 plays a critical role in telomerase-independent telomere maintenance. Thus, we uncover roles for kinesin and NPCs in DNA repair by BIR and reveal that perinuclear telomere anchors license subtelomeric DSBs for this error-prone DNA repair mechanism.

show abstract

Section: Discussionsupporting

confidence: 70%

Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Microtubules show dynamic instability, interconversion of assembly and disassembly. [4][5][6] The posttranslational modification of tubulin, such as deacetylation, detyrosination, phosphorylation and polyglutamation, is involved in the regulation of microtubule dynamics and microtubule-based cellular functions such as cell morphology, cell survival and cell migration. Acetylation of a-tubulin on lysine-40 has been implicated in the regulation of microtubule stability and structure, as well as microtubule-based cellular functions, suggesting that acetylation is one of the most important modifications of tubulin.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II induces microtubule reorganization mediated by a deacetylase SIRT2 in endothelial cells

et al. 2011

View full text Add to dashboard Cite

Angiotensin II has been implicated in vascular remodeling. Microtubule composed of tubulins regulates cell shape, migration and survival. Tubulin acetylation has an important role in the control of microtubule structure and microtubule-based cellular functions. In this study, angiotensin II induced disassembly and deacetylation of a-tubulin, which were blocked by pretreatment with an angiotensin II type 1 receptor blocker losartan and a sirtuin class deacetylase inhibitor sirtinol, and by depletion of a deacetylase SIRT2 using RNA interference. We investigated the involvement of SIRT2 in angiotensin II-induced endothelial cell migration using the Boyden chamber method. Angiotensin II caused a significant increase in cell migration, which was blocked by pretreatment with sirtinol and SIRT2 depletion. It has been reported that angiotensin II is involved in cytoskeletal reorganization stimulated by mechanical stretch in endothelial cells. We also demonstrated that endothelial cells subjected to a 10% uniaxial stretch showed vertical alignment to the direction of tension and tubulin deacetylation in the peripheral side of cells, in comparison with control static cells. The mechanical stretch-induced changes of microtubules were blocked by pretreatment with sirtinol and SIRT2 depletion. Immunofluorescence microscopy showed that acetylated tubulin was decreased in platelet-endothelial cell adhesion molecule-1-positive cells in the intima of the aortic walls in mice loaded with angiotensin II, in comparison with mice loaded with control vehicle. These data show that angiotensin II and mechanical stretch stimulate microtubule redistribution and deacetylation via SIRT2 in endothelial cells, suggesting the emerging role of SIRT2 in hypertension-induced vascular remodeling.

show abstract

“…Miscellaneous information about microtubules in C. elegans epithelia GENERAL BACKGROUND Microtubules are 25 nm wide hollow and rigid polymers assembled from a-tubulin and ß-tubulin heterodimers, which belong to guanosine-5'-triphosphate (GTP) hydrolase super-family. The binding of tubulin to GTP or GDP induces a conformational change that confers growth or shrinkage to microtubules (Brouhard, 2015;Howard and Hyman, 2003;Mitchison and Kirschner, 1984). In most eukaryotic cell types microtubules are assembled from 13 protofilaments, although C. elegans cells generally contain 11 protofilaments and their touch neurons 15 protofilaments.…”

Section: Noncentrosomal Microtubules Mediate Nuclear Positioningmentioning

confidence: 99%

“…In most eukaryotic cell types microtubules are assembled from 13 protofilaments, although C. elegans cells generally contain 11 protofilaments and their touch neurons 15 protofilaments. Microtubules are polar filaments: they are nucleated at their rather stable minus-end with an exposed a-tubulin subunit, whereas they actively polymerise and depolymerize at their plus-end bearing an exposed ß-tubulin subunit (Mitchison and Kirschner, 1984). Proteins influencing their dynamic behaviour include the microtubule-organizing centres and minusend binding proteins, plus-end binding proteins, specific chaperonins, Microtubule Associated Proteins (MAPs) and motor proteins (Akhmanova and Hoogenraad, 2015;Akhmanova and Steinmetz, 2008).…”

Section: Noncentrosomal Microtubules Mediate Nuclear Positioningmentioning

confidence: 99%

Noncentrosomal microtubules in C. elegans epithelia

Quintin

Gally

Labouesse

2016

Genesis

View full text Add to dashboard Cite

Summary:The microtubule cytoskeleton has a dual contribution to cell organization. First, microtubules help displace chromosomes and provide tracks for organelle transport. Second, microtubule rigidity confers specific mechanical properties to cells, which are crucial in cilia or mechanosensory structures. Here we review the recently uncovered organization and functions of noncentrosomal microtubules in C. elegans epithelia, focusing on how they contribute to nuclear positioning and protein transport. In addition, we describe recent data illustrating how the microtubule and actin cytoskeletons interact to achieve those functions. genesis 54:229-242, 2016. V C 2016 Wiley Periodicals, Inc.

show abstract

Dynamic instability of microtubule growth

Abstract: We report here that microtubules in vitro coexist in growing and shrinking populations which interconvert rather infrequently. This dynamic instability is a general property of microtubules and may be fundamental in explaining cellular microtubule organization.

Cited by 3,055 publications

References 16 publications

Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process

Perinuclear tethers license telomeric DSBs for a broad kinesin- and NPC-dependent DNA repair process

Angiotensin II induces microtubule reorganization mediated by a deacetylase SIRT2 in endothelial cells

Noncentrosomal microtubules in C. elegans epithelia

Contact Info

Product

Resources

About