Tubulin modifications and their cellular functions

Hammond, Jennetta W.; Cai, Dawen; Verhey, Kristen J.

doi:10.1016/j.ceb.2007.11.010

Cited by 449 publications

(392 citation statements)

References 49 publications

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“…39 Several factors have been postulated to affect the dynamics of the microtubule system. Tubulin is subjected to a number of post-translational modifications, such as phosphorylation, acetylation, tyrosination, polyglycylation, and polyglutamylation, 25 which influence the stability and structure of MT assemblies and thereby alter the dynamic properties and cellular functions of MTs. 40 Acetylation of the Lys40 residue in a-tubulin is a well-noted MT modification, and acetylated a-tubulin (Ac-tubulin) is enriched at interpolar and kinetochore MTs in mitotic cells.…”

Section: Discussionmentioning

confidence: 99%

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EWSR1 regulates mitosis by dynamically influencing microtubule acetylation

et al. 2016

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EWSR1, participating in transcription and splicing, has been identified as a translocation partner for various transcription factors, resulting in translocation, which in turn plays crucial roles in tumorigenesis. Recent studies have investigated the role of EWSR1 in mitosis. However, the effect of EWSR1 on mitosis is poorly understood. Here, we observed that depletion of EWSR1 resulted in cell cycle arrest in the mitotic phase, mainly due to an increase in the time from nuclear envelope breakdown to metaphase, resulting in a high percentage of unaligned chromosomes and multipolar spindles. We also demonstrated that EWSR1 is a spindle-associated protein that interacts with a-tubulin during mitosis. EWSR1 depletion increased the cold-sensitivity of spindle microtubules, and decreased the rate of spindle assembly. EWSR1 regulated the level of microtubule acetylation in the mitotic spindle; microtubule acetylation was rescued in EWSR1-depleted mitotic cells following suppression of HDAC6 activity by its specific inhibitor or siRNA treatment. In summary, these results suggest that EWSR1 regulates the acetylation of microtubules in a cell cycledependent manner through its dynamic location on spindle MTs, and may be a novel regulator for mitosis progress independent of its translocation.

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Section: Discussionmentioning

confidence: 99%

“…25 However, knockdown of EWSR1 did not change the detyrosination and polyglutamylation levels of tubulin in mitotic cells (Fig. 5F).…”

Section: Knockdown Of Ewsr1 Decreases A-tubulin Acetylationmentioning

confidence: 99%

EWSR1 regulates mitosis by dynamically influencing microtubule acetylation

et al. 2016

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“…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. 7,8 Silent information regulator 2 was identified in Saccharomyces cerevisiae as a nicotinamide adenine dinucleotide + -dependent histone deacetylase. Seven homologs of silent information regulator 2 have been identified in mammals and designated as SIRT1-7.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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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.

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“…The third group contains proteins that modulate MT number, such as regulators of nucleation (Luders and Stearns 2007), enzymes that sever preexisting MTs (Roll-Mecak and McNally 2010; Sharp and Ross 2012), and minus-end targeting proteins (-TIPs), stabilizing minus ends (Akhmanova and Hoogenraad 2015). The fourth set comprises tubulin-modifying enzymes that, through posttranslational modifications, can generate distinct MT subtypes (Hammond et al 2008;Janke and Bulinski 2011). The fifth group includes cross-linking proteins that align filaments and form MT bundles, such as classical MAPs and some kinesin motors that drive MT sliding (Bratman and Chang 2008;Dehmelt and Halpain 2005;Maccioni and Cambiazo 1995).…”

Section: Introductionmentioning

confidence: 99%

Microtubule Organization and Microtubule-Associated Proteins (MAPs)

2016

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Dendrites have a unique microtubule organization. In vertebrates, dendritic microtubules are organized in antiparallel bundles, oriented with their plus ends either pointing away or toward the soma. The mixed microtubule arrays control intracellular trafficking and local signaling pathways, and are essential for dendrite development and function. The organization of microtubule arrays largely depends on the combined function of different microtubule regulatory factors or generally named microtubule-associated proteins (MAPs). Classical MAPs, also called structural MAPs, were identified more than 20 years ago based on their ability to bind to and copurify with microtubules. Most classical MAPs bind along the microtubule lattice and regulate microtubule polymerization, bundling, and stabilization. Recent evidences suggest that classical MAPs also guide motor protein transport, interact with the actin cytoskeleton, and act in various neuronal signaling networks. Here, we give an overview of microtubule organization in dendrites and the role of classical MAPs in dendrite development, dendritic spine formation, and synaptic plasticity. IntroductionMicrotubules (MTs) are cytoskeletal structures that play essential roles in all eukaryotic cells. MTs are important not only during cell division but also in non-dividing cells, where they are critical structures in numerous cellular processes such as cell motility, migration, differentiation, intracellular transport and organelle positioning. MTs are composed of two proteins, α-and β-tubulin, that form heterodimers and organize themselves in a head-to-tail manner. MTs are dynamic and they can rapidly switch between cycles of growth and shrinkage. This MT

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Tubulin modifications and their cellular functions

Cited by 449 publications

References 49 publications

EWSR1 regulates mitosis by dynamically influencing microtubule acetylation

EWSR1 regulates mitosis by dynamically influencing microtubule acetylation

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

Microtubule Organization and Microtubule-Associated Proteins (MAPs)

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