期刊
JOURNAL OF NEUROSCIENCE
卷 28, 期 48, 页码 12993-13002出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2860-08.2008
关键词
parkin; HDAC6; proteasome; aggresome; microtubule; Parkinson's disease
资金
- National Institutes of Health [NS4172]
- New York State Center of Excellence in Bioinformatics and Life Sciences
Histone deacetylase 6 ( HDAC6), a microtubule-associated tubulin deacetylase, plays a significant role in the formation of protein aggregates in many neurodegenerative disorders. Parkin, a protein-ubiquitin E3 ligase linked to Parkinson's disease, accumulates at the centrosome in a microtubule-dependent manner in response to proteasome inhibition. Here, we show that the centrosome recruitment of parkin was mediated by its direct binding to HDAC6 through multiple interaction domains. The tubulin deacetylase activity of HDAC6 was required for the accumulation of parkin as well as its dispersion upon the reversal of proteasome inhibition. The bidirectional movements of parkin required intact microtubule network and were dependent on dynein and kinesin 1, respectively. Tubulin deacetylation increases microtubule dynamicity and may thus facilitate microtubule-based trafficking of the parkin-HDAC6 complex. The results suggest that HDAC6 acts as a sensor of proteasome inhibition and directs the trafficking of parkin by using different motor proteins.
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