HDAC6 modulates cell motility by altering the acetylation level of cortactin

Mol Cell. 2007 Jul 20;27(2):197-213. doi: 10.1016/j.molcel.2007.05.033.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Actins / metabolism
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Cell Cycle Proteins / metabolism
  • Cell Movement / physiology*
  • Cortactin / chemistry
  • Cortactin / genetics
  • Cortactin / metabolism*
  • HeLa Cells
  • Histone Acetyltransferases / metabolism
  • Histone Deacetylase 6
  • Histone Deacetylase Inhibitors
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • In Vitro Techniques
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • NIH 3T3 Cells
  • Protein Binding
  • Rabbits
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Repetitive Sequences, Amino Acid
  • Sequence Homology, Amino Acid
  • Transcription Factors / metabolism
  • p300-CBP Transcription Factors


  • Actins
  • CTTN protein, human
  • Cell Cycle Proteins
  • Cortactin
  • Cttn protein, mouse
  • Histone Deacetylase Inhibitors
  • Recombinant Proteins
  • Transcription Factors
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • HDAC6 protein, human
  • Histone Deacetylase 6
  • Histone Deacetylases

Associated data

  • PDB/2F9X