QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 26, 2008, 28(48):12993-13002; doi:10.1523/JNEUROSCI.2860-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jiang, Q. Articles by Feng, J. Search for Related Content PubMed PubMed Citation Articles by Jiang, Q. Articles by Feng, J.

 Previous Article  |  Next Article 

Neurobiology of Disease
Direct Binding with Histone Deacetylase 6 Mediates the Reversible Recruitment of Parkin to the Centrosome

Qian Jiang,^1,2 Yong Ren,^1,2 and Jian Feng^1,2

¹Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York 14214, and ²Neurodegenerative Disease Group, New York State Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, Buffalo, New York 14203

Correspondence should be addressed to Dr. Jian Feng, Department of Physiology and Biophysics, State University of New York, Buffalo, 124 Sherman Hall, Buffalo, NY 14214. Email: jianfeng{at}buffalo.edu

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.

Key words: parkin; HDAC6; proteasome; aggresome; microtubule; Parkinson's disease

---

Received June 22, 2008; accepted Oct. 22, 2008.

Correspondence should be addressed to Dr. Jian Feng, Department of Physiology and Biophysics, State University of New York, Buffalo, 124 Sherman Hall, Buffalo, NY 14214. Email: jianfeng{at}buffalo.edu

This article has been cited by other articles:

				Y. Zilberman, C. Ballestrem, L. Carramusa, R. Mazitschek, S. Khochbin, and A. Bershadsky Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6 J. Cell Sci., October 1, 2009; 122(19): 3531 - 3541. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help