The Hsp90 cochaperone, FKBP51, increases Tau stability and polymerizes microtubules.
The Hsp90 cochaperone, FKBP51, increases Tau stability and polymerizes microtubules.
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DOI：
10.1523/jneurosci.4815-09.2010
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发表时间：
2010-01-13
期刊：
影响因子：
--
通讯作者：
Dickey CA
中科院分区：
文献类型：
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作者：
Jinwal UK;Koren J 3rd;Borysov SI;Schmid AB;Abisambra JF;Blair LJ;Johnson AG;Jones JR;Shults CL;O'Leary JC 3rd;Jin Y;Buchner J;Cox MB;Dickey CA
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 (AD). Here, we show that the Hsp90 cochaperone, FK506 binding protein 51 (FKBP51), which possesses both an Hsp90 interacting tetratricopeptide (TPR) domain and a cis-trans 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 utilize the Hsp90 complex to isomerize tau, altering its phosphorylation pattern and stabilizing microtubules.
