Class V ?-tubulin alters dynamic instability and stimulates microtubule detachment from centrosomes.

ABSTRACT: A multigene family produces tubulin isotypes that are expressed in a tissue-specific manner, but the role of these isotypes in microtubule assembly and function is unclear. Recently we showed that overexpression or depletion of ?5-tubulin, a minor isotype with wide tissue distribution, inhibits cell division. We now report that elevated ?5-tubulin causes uninterrupted episodes of microtubule shortening and increased shortening rates. Conversely, depletion of ?5-tubulin reduces shortening rates and causes very short excursions of growth and shortening. A tubulin conformation-sensitive antibody indicated that the uninterrupted shortening can be explained by a relative absence of stabilized patches along the microtubules that contain tubulin in an assembly-competent conformation and normally act to restore microtubule growth. In addition to these changes in dynamic instability, overexpression of ?5-tubulin causes fragmentation that results from microtubule detachment from centrosomes, and it is this activity that best explains the effects of ?5 on cell division. Paclitaxel inhibits microtubule detachment, increases the number of assembly-competent tubulin patches, and inhibits microtubule shortening, thus providing an explanation for why the drug can counteract the phenotypic effects of ?5 overexpression. On the basis of these observations, we propose that cells can use ?5-tubulin expression to adjust the behavior of the microtubule cytoskeleton.

SUBMITTER: Bhattacharya R 

PROVIDER: S-EPMC3069006 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature