HDAC6 modulates cell motility by altering the acetylation level of cortactin.

Published

Journal Article

Histone deacetylase 6 (HDAC6) is a tubulin-specific deacetylase that regulates microtubule-dependent cell movement. In this study, we identify the F-actin-binding protein cortactin as a HDAC6 substrate. We demonstrate that HDAC6 binds cortactin and that overexpression of HDAC6 leads to hypoacetylation of cortactin, whereas inhibition of HDAC6 activity leads to cortactin hyperacetylation. HDAC6 alters the ability of cortactin to bind F-actin by modulating a "charge patch" in its repeat region. Introduction of charge-preserving or charge-neutralizing mutations in this cortactin repeat region correlates with the gain or loss of F-actin binding ability, respectively. Cells expressing a charge-neutralizing cortactin mutant were less motile than control cells or cells expressing a charge-preserving mutant. These findings suggest that, in addition to its role in microtubule-dependent cell motility, HDAC6 influences actin-dependent cell motility by altering the acetylation status of cortactin, which, in turn, changes the F-actin binding activity of cortactin.

Full Text

Duke Authors

Cited Authors

  • Zhang, X; Yuan, Z; Zhang, Y; Yong, S; Salas-Burgos, A; Koomen, J; Olashaw, N; Parsons, JT; Yang, X-J; Dent, SR; Yao, T-P; Lane, WS; Seto, E

Published Date

  • July 20, 2007

Published In

Volume / Issue

  • 27 / 2

Start / End Page

  • 197 - 213

PubMed ID

  • 17643370

Pubmed Central ID

  • 17643370

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2007.05.033

Language

  • eng

Conference Location

  • United States