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 Sheetz, Tso Pang Yao, Chloë C. Bulinski

Research output: Contribution to journalArticle

194 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Histone Deacetylases
Tubulin
Microtubules
Focal Adhesions
Cell Movement
Photobleaching
NAD
Pharmacology

Keywords

  • Acetylation
  • Dynamics
  • Focal adhesion
  • HDAC6
  • Microtubule

ASJC Scopus subject areas

  • Cell Biology

Cite this

Tran, A. D. A., Marmo, T. P., Salam, A. A., Che, S., Finkelstein, E., Kabarriti, R., ... 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

HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions. / Tran, Andy Dong Anh; Marmo, Timothy P.; Salam, Ambar A.; Che, Sally; Finkelstein, Erik; Kabarriti, Rafi; Xenias, Harry S.; Mazitschek, Ralph; Hubbert, Charlotte; Kawaguchi, Yoshiharu; Sheetz, Michael; Yao, Tso Pang; Bulinski, Chloë C.

In: Journal of Cell Science, Vol. 120, No. 8, 15.04.2007, p. 1469-1479.

Research output: Contribution to journalArticle

Tran, ADA, Marmo, TP, Salam, AA, Che, S, Finkelstein, E, Kabarriti, R, Xenias, HS, Mazitschek, R, Hubbert, C, Kawaguchi, Y, Sheetz, M, Yao, TP & Bulinski, CC 2007, 'HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions', Journal of Cell Science, vol. 120, no. 8, pp. 1469-1479. https://doi.org/10.1242/jcs.03431
Tran ADA, Marmo TP, Salam AA, Che S, Finkelstein E, Kabarriti R et al. HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions. Journal of Cell Science. 2007 Apr 15;120(8):1469-1479. https://doi.org/10.1242/jcs.03431
Tran, Andy Dong Anh ; Marmo, Timothy P. ; Salam, Ambar A. ; Che, Sally ; Finkelstein, Erik ; Kabarriti, Rafi ; Xenias, Harry S. ; Mazitschek, Ralph ; Hubbert, Charlotte ; Kawaguchi, Yoshiharu ; Sheetz, Michael ; Yao, Tso Pang ; Bulinski, Chloë C. / HDAC6 deacetylation of tubulin modulates dynamics of cellular adhesions. In: Journal of Cell Science. 2007 ; Vol. 120, No. 8. pp. 1469-1479.
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