HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions

Andy Dong Anh Tran, Timothy P. Marmo, Ambar A. Salam, Sally Che, Erik Finkelstein, Rafi Kabarriti, Harry S. Xenias, Ralph Mazitschek, Charlotte Hubbert, Yoshiharu Kawaguchi, Michael P. Sheetz, Tso Pang Yao, Chloë C. Bulinski

Research output: Contribution to journalArticle

201 Scopus citations

Abstract

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 α-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.

Original languageEnglish (US)
Pages (from-to)1469-1479
Number of pages11
JournalJournal of cell science
Volume120
Issue number8
DOIs
StatePublished - Apr 15 2007

Keywords

  • Acetylation
  • Dynamics
  • Focal adhesion
  • HDAC6
  • Microtubule

ASJC Scopus subject areas

  • Cell Biology

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    Tran, A. D. A., Marmo, T. P., Salam, A. A., Che, S., Finkelstein, E., Kabarriti, R., Xenias, H. S., Mazitschek, R., Hubbert, C., Kawaguchi, Y., Sheetz, M. P., Yao, T. P., & Bulinski, C. C. (2007). HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions. Journal of cell science, 120(8), 1469-1479. https://doi.org/10.1242/jcs.03431