Histone deacetylase 6 regulates growth factor-induced actin remodeling and endocytosis.

Published

Journal Article

Histone deacetylase 6 (HDAC6) is a cytoplasmic deacetylase that uniquely catalyzes alpha-tubulin deacetylation and promotes cell motility. However, the mechanism underlying HDAC6-dependent cell migration and the role for microtubule acetylation in motility are not known. Here we show that HDAC6-induced global microtubule deacetylation was not sufficient to stimulate cell migration. Unexpectedly, in response to growth factor stimulation, HDAC6 underwent rapid translocation to actin-enriched membrane ruffles and subsequently became associated with macropinosomes, the vesicles for fluid-phase endocytosis. Supporting the importance of these associations, membrane ruffle formation, macropinocytosis, and cell migration were all impaired in HDAC6-deficient cells. Conversely, elevated HDAC6 levels promoted membrane ruffle formation with a concomitant increase in macropinocytosis and motility. In search for an HDAC6 target, we found that heat shock protein 90 (Hsp90), another prominent substrate of HDAC6, was also recruited to membrane ruffles and macropinosomes. Significantly, inhibition of Hsp90 activity suppressed membrane ruffling and cell migration, while expression of an acetylation-resistant Hsp90 mutant promoted ruffle formation. Our results uncover a surprising role for HDAC6 in actin remodeling-dependent processes and identify the actin cytoskeleton as an important target of HDAC6-regulated protein deacetylation.

Full Text

Duke Authors

Cited Authors

  • Gao, Y-S; Hubbert, CC; Lu, J; Lee, Y-S; Lee, J-Y; Yao, T-P

Published Date

  • December 2007

Published In

Volume / Issue

  • 27 / 24

Start / End Page

  • 8637 - 8647

PubMed ID

  • 17938201

Pubmed Central ID

  • 17938201

Electronic International Standard Serial Number (EISSN)

  • 1098-5549

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/MCB.00393-07

Language

  • eng