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Histone deacetylase 6 interacts with the microtubule‐associated protein tau
Author(s) -
Ding Huiping,
Dolan Philip J.,
Johnson Gail V. W.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05564.x
Subject(s) - hdac6 , aggresome , tauopathy , neurodegeneration , microtubule , microbiology and biotechnology , acetylation , histone deacetylase , tau protein , hdac10 , biology , phosphorylation , microtubule associated protein , chemistry , tubulin , alzheimer's disease , histone , biochemistry , ubiquitin , medicine , disease , pathology , gene
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.