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Histone deacetylase 6 interacts with the microtubule-associated protein tau.

Histone deacetylase 6 (HDAC6), a unique cytoplasmic deacetylase, likely plays a role in neurodegeneration by coordinating cell responses to abnormal protein aggregation. Here, we provide in vitro and in vivo evidence that HDAC6 interacts with tau, a microtubule-associated protein that forms neurofibrillary tangles in Alzheimer's disease. This interaction is mediated by the microtubule-binding domain on tau and the Ser/Glu tetradecapeptide domain on HDAC6. Treatment with tubacin, a selective inhibitor of tubulin deacetylation activity of HDAC6, did not disrupt HDAC6-tau interaction. Nonetheless tubacin treatment attenuated site-specific tau phosphorylation, as did shRNA-mediated knockdown of HDAC6. Proteasome inhibition potentiated HDAC6-tau interactions and facilitated the concentration and co-localization of HDAC6 and tau in a perinuclear aggresome-like compartment, independent of HDAC6 tubulin deacetylase activity. Furthermore, we observed that in Alzheimer's disease brains the protein level of HDAC6 was significantly increased. These findings establish HDAC6 as a tau-interacting protein and as a potential modulator of tau phosphorylation and accumulation.

Pubmed ID: 18636984

Authors

  • Ding H
  • Dolan PJ
  • Johnson GV

Journal

Journal of neurochemistry

Publication Data

September 17, 2008

Associated Grants

  • Agency: NINDS NIH HHS, Id: NS051279
  • Agency: NIA NIH HHS, Id: P50 AG16582
  • Agency: NINDS NIH HHS, Id: R01 NS051279
  • Agency: NINDS NIH HHS, Id: R01 NS051279-04

Mesh Terms

  • Aged
  • Alzheimer Disease
  • Anilides
  • Brain
  • Cell Compartmentation
  • Cell Line
  • Down-Regulation
  • Enzyme Inhibitors
  • Female
  • Histone Deacetylases
  • Humans
  • Hydroxamic Acids
  • Male
  • Microtubules
  • Middle Aged
  • Neurofibrillary Tangles
  • Neurons
  • Organelles
  • Phosphorylation
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Small Interfering
  • tau Proteins