Motor-dependent microtubule disassembly driven by tubulin tyrosination

Author:

Peris Leticia123,Wagenbach Michael4,Lafanechère Laurence235,Brocard Jacques123,Moore Ayana T.4,Kozielski Frank6,Job Didier123,Wordeman Linda4,Andrieux Annie123

Affiliation:

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 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

3. Université Joseph Fourier, 38042 Grenoble, Cedex 9, France

4. Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195

5. Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5168, 38054 Grenoble, Cedex 9, France

6. The Beatson Institute for Cancer Research, Glasgow G61 1BD, Scotland, UK

Abstract

In cells, stable microtubules (MTs) are covalently modified by a carboxypeptidase, which removes the C-terminal Tyr residue of α-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.

Publisher

Rockefeller University Press

Subject

Cell Biology

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