Journal article
The Hsp90 Cochaperone, FKBP51, Increases Tau Stability and Polymerizes Microtubules
The Journal of neuroscience, v 30(2), pp 591-599
13 Jan 2010
PMID: 20071522
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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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Details
- Title
- The Hsp90 Cochaperone, FKBP51, Increases Tau Stability and Polymerizes Microtubules
- Creators
- Umesh K. Jinwal - Univ S Florida, Johnnie B Byrd Sr Alzheimers Res Inst, Tampa, FL 33613 USAJohn Koren - Univ S Florida, Johnnie B Byrd Sr Alzheimers Res Inst, Tampa, FL 33613 USASergiy I. Borysov - Univ S Florida, Johnnie B Byrd Sr Alzheimers Res Inst, Tampa, FL 33613 USAAndreas B. Schmid - Ludwig Maximilian University of MunichJose F. Abisambra - Univ S Florida, Johnnie B Byrd Sr Alzheimers Res Inst, Tampa, FL 33613 USALaura J. Blair - Univ S Florida, Johnnie B Byrd Sr Alzheimers Res Inst, Tampa, FL 33613 USAAmelia G. Johnson - Univ S Florida, Johnnie B Byrd Sr Alzheimers Res Inst, Tampa, FL 33613 USAJeffrey R. Jones - Univ S Florida, Johnnie B Byrd Sr Alzheimers Res Inst, Tampa, FL 33613 USACody L. Shults - Univ S Florida, Johnnie B Byrd Sr Alzheimers Res Inst, Tampa, FL 33613 USAJohn C. O'Leary - Univ S Florida, Johnnie B Byrd Sr Alzheimers Res Inst, Tampa, FL 33613 USAYing Jin - Univ S Florida, Johnnie B Byrd Sr Alzheimers Res Inst, Tampa, FL 33613 USAJohannes Buchner - Ludwig Maximilian University of MunichMarc B. Cox - Biological SciencesChad A. Dickey - Univ S Florida, Johnnie B Byrd Sr Alzheimers Res Inst, Tampa, FL 33613 USA
- Publication Details
- The Journal of neuroscience, v 30(2), pp 591-599
- Publisher
- Soc Neuroscience
- Number of pages
- 9
- Grant note
- Rosalinde and Arthur Gilbert Foundation/American Federation for Aging Research R00AG031291 / National Institute on Aging; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) CompInt program of the Elitenetzwerk Bayern CurePSP
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000273586900018
- Scopus ID
- 2-s2.0-74949110831
- Other Identifier
- 991020545238504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Neurosciences