HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions.

Published

Journal Article

Genetic or pharmacological alteration of the activity of the histone deacetylase 6 (HDAC6) induces a parallel alteration in cell migration. Using tubacin to block deacetylation of alpha-tubulin, and not other HDAC6 substrates, yielded a motility reduction equivalent to agents that block all NAD-independent HDACs. Accordingly, we investigated how the failure to deacetylate tubulin contributes to decreased motility in HDAC6-inhibited cells. Testing the hypothesis that motility is reduced because cellular adhesion is altered, we found that inhibiting HDAC6 activity towards tubulin rapidly increased total adhesion area. Next, we investigated the mechanism of the adhesion area increase. Formation of adhesions proceeded normally and cell spreading was more rapid in the absence of active HDAC6; however, photobleaching assays and adhesion breakdown showed that adhesion turnover was slower. To test the role of hyperacetylated tubulin in altering adhesion turnover, we measured microtubule dynamics in HDAC6-inhibited cells because dynamic microtubules are required to target adhesions for turnover. HDAC6 inhibition yielded a decrease in microtubule dynamics that was sufficient to decrease focal adhesion turnover. Thus, our results suggest a scenario in which the decreased dynamics of hyperacetylated microtubules in HDAC6-inhibited cells compromises their capacity to mediate the focal adhesion dynamics required for rapid cell migration.

Full Text

Duke Authors

Cited Authors

  • Tran, AD-A; Marmo, TP; Salam, AA; Che, S; Finkelstein, E; Kabarriti, R; Xenias, HS; Mazitschek, R; Hubbert, C; Kawaguchi, Y; Sheetz, MP; Yao, T-P; Bulinski, JC

Published Date

  • April 2007

Published In

Volume / Issue

  • 120 / Pt 8

Start / End Page

  • 1469 - 1479

PubMed ID

  • 17389687

Pubmed Central ID

  • 17389687

Electronic International Standard Serial Number (EISSN)

  • 1477-9137

International Standard Serial Number (ISSN)

  • 0021-9533

Digital Object Identifier (DOI)

  • 10.1242/jcs.03431

Language

  • eng