Dysferlin interacts with histone deacetylase 6 and increases alpha-tubulin acetylation

PLoS One. 2011;6(12):e28563. doi: 10.1371/journal.pone.0028563. Epub 2011 Dec 8.


Dysferlin is a multi-C2 domain transmembrane protein involved in a plethora of cellular functions, most notably in skeletal muscle membrane repair, but also in myogenesis, cellular adhesion and intercellular calcium signaling. We previously showed that dysferlin interacts with alpha-tubulin and microtubules in muscle cells. Microtubules are heavily reorganized during myogenesis to sustain growth and elongation of the nascent muscle fiber. Microtubule function is regulated by post-translational modifications, such as acetylation of its alpha-tubulin subunit, which is modulated by the histone deacetylase 6 (HDAC6) enzyme. In this study, we identified HDAC6 as a novel dysferlin-binding partner. Dysferlin prevents HDAC6 from deacetylating alpha-tubulin by physically binding to both the enzyme, via its C2D domain, and to the substrate, alpha-tubulin, via its C2A and C2B domains. We further show that dysferlin expression promotes alpha-tubulin acetylation, as well as increased microtubule resistance to, and recovery from, Nocodazole- and cold-induced depolymerization. By selectively inhibiting HDAC6 using Tubastatin A, we demonstrate that myotube formation was impaired when alpha-tubulin was hyperacetylated early in the myogenic process; however, myotube elongation occurred when alpha-tubulin was hyperacetylated in myotubes. This study suggests a novel role for dysferlin in myogenesis and identifies HDAC6 as a novel dysferlin-interacting protein.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Acetylation
  • Animals
  • Cell Differentiation
  • Cell Line
  • Dysferlin
  • Histone Deacetylase 6
  • Histone Deacetylases / metabolism*
  • Humans
  • Immunoprecipitation
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mice
  • Microtubules / metabolism
  • Muscle Development
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / enzymology
  • Muscle Proteins / chemistry
  • Muscle Proteins / metabolism*
  • Polymerization
  • Protein Binding
  • Protein Structure, Tertiary
  • Tubulin / metabolism*


  • DYSF protein, human
  • Dysf protein, mouse
  • Dysferlin
  • Membrane Proteins
  • Muscle Proteins
  • Tubulin
  • HDAC6 protein, human
  • Hdac6 protein, mouse
  • Histone Deacetylase 6
  • Histone Deacetylases