Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2794K) PDF+supp data (5085K) PPT slides of all figures Supplemental Material Related biosights video Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Peris, L. Articles by Andrieux, A. PubMed PubMed Citation Articles by Peris, L. Articles by Andrieux, A. Related Collections Related In this Issue article Social Bookmarking                            What's this?

Motor-dependent microtubule disassembly driven by tubulin tyrosination

¹ Institut National de la Santé et de la Recherche Medicale Unité 836, Institut des Neurosciences de Grenoble, 38042 Grenoble, Cedex 9, France
² Groupe Physiopathologie du Cytosquelette and ³ Criblage pour Molécules Bio-Actives, Institut de Recherches en Technologies et Sciences pour le Vivant, Direction des Sciences du Vivant, Commissariat à l'Énergie Atomique, 38054 Grenoble, Cedex 9, France
⁴ Université Joseph Fourier, 38042 Grenoble, Cedex 9, France
⁵ Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195
⁶ Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5168, 38054 Grenoble, Cedex 9, France
⁷ The Beatson Institute for Cancer Research, Glasgow G61 1BD, Scotland, UK

Correspondence to Leticia Peris: Leticia.peris{at}ujf-grenoble.fr; or Annie Andrieux: annie.andrieux{at}ujf-grenoble.fr

In cells, stable microtubules (MTs) are covalently modified by a carboxypeptidase, which removes the C-terminal Tyr residue of -tubulin. The significance of this selective detyrosination of MTs is not understood. In this study, we report that tubulin detyrosination in fibroblasts inhibits MT disassembly. This inhibition is relieved by overexpression of the depolymerizing motor mitotic centromere-associated kinesin (MCAK). Conversely, suppression of MCAK expression prevents disassembly of normal tyrosinated MTs in fibroblasts. Detyrosination of MTs suppresses the activity of MCAK in vitro, apparently as the result of a decreased affinity of the adenosine diphosphate (ADP)–inorganic phosphate- and ADP-bound forms of MCAK for the MT lattice. Detyrosination also impairs MT disassembly in neurons and inhibits the activity of the neuronal depolymerizing motor KIF2A in vitro. These results indicate that MT depolymerizing motors are directly inhibited by the detyrosination of tubulin, resulting in the stabilization of cellular MTs. Detyrosination of transiently stabilized MTs may give rise to persistent subpopulations of disassembly-resistant polymers to sustain subcellular cytoskeletal differentiation.

© 2009 Peris et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Zilberman, Y., Ballestrem, C., Carramusa, L., Mazitschek, R., Khochbin, S., Bershadsky, A. (2009). Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6. J. Cell Sci. 122: 3531-3541 [Abstract] [Full Text]  
• Short, B. (2009). Bringing stability to microtubules. JCB 185: 1130-1130 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents