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The Journal of Neuroscience, January 13, 2010, 30(2):591-599; doi:10.1523/JNEUROSCI.4815-09.2010

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Neurobiology of Disease
The Hsp90 Cochaperone, FKBP51, Increases Tau Stability and Polymerizes Microtubules

Umesh K. Jinwal,¹ John Koren III,¹ Sergiy I. Borysov,¹ Andreas B. Schmid,² Jose F. Abisambra,¹ Laura J. Blair,¹ Amelia G. Johnson,¹ Jeffrey R. Jones,¹ Cody L. Shults,¹ John C. O'Leary III,¹ Ying Jin,¹ Johannes Buchner,² Marc B. Cox,³ and Chad A. Dickey¹

¹Johnnie B. Byrd Sr. Alzheimer's Research Institute and Department of Molecular Medicine, University of South Florida, Tampa, Florida 33613, ²Lehrstuhl für Biotechnologie, Department Chemie, Technische Universität München, 85747 Garching, Germany, and ³Border Biomedical Research Center and Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas 79968

Correspondence should be addressed to Dr. Chad A. Dickey, University of South Florida, 4001 East Fletcher Avenue, MDC 36, Tampa, FL 33613. Email: cdickey{at}health.usf.edu

Imbalanced protein load within cells is a critical aspect for most diseases of aging. In particular, the accumulation of proteins into neurotoxic aggregates is a common thread for a host of neurodegenerative diseases. Our previous work demonstrated that age-related changes to the cellular chaperone repertoire contributes to abnormal buildup of the microtubule-associated protein tau that accumulates in a group of diseases termed tauopathies, the most common being Alzheimer's disease. Here, we show that the Hsp90 cochaperone, FK506-binding protein 51 (FKBP51), which possesses both an Hsp90-interacting tetratricopeptide domain and a peptidyl-prolyl cis-trans isomerase (PPIase) domain, prevents tau clearance and regulates its phosphorylation status. Regulation of the latter is dependent on the PPIase activity of FKBP51. FKB51 enhances the association of tau with Hsp90, but the FKBP51/tau interaction is not dependent on Hsp90. In vitro FKBP51 stabilizes microtubules with tau in a reaction depending on the PPIase activity of FKBP51. Based on these new findings, we propose that FKBP51 can use the Hsp90 complex to isomerize tau, altering its phosphorylation pattern and stabilizing microtubules.

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Received Sept. 28, 2009; revised Oct. 24, 2009; accepted Nov. 11, 2009.

Correspondence should be addressed to Dr. Chad A. Dickey, University of South Florida, 4001 East Fletcher Avenue, MDC 36, Tampa, FL 33613. Email: cdickey{at}health.usf.edu

This article has been cited by other articles:

				U. K. Jinwal, J. C. O'Leary III, S. I. Borysov, J. R. Jones, Q. Li, J. Koren III, J. F. Abisambra, G. D. Vestal, L. Y. Lawson, A. G. Johnson, et al. Hsc70 Rapidly Engages Tau after Microtubule Destabilization J. Biol. Chem., May 28, 2010; 285(22): 16798 - 16805. [Abstract] [Full Text] [PDF]

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