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J Neurosci. January 13, 2010; 30 (2): 591-9.

The Hsp90 cochaperone, FKBP51, increases Tau stability and polymerizes microtubules.

Jinwal UK , Koren J , Borysov SI , Schmid AB , Abisambra JF , Blair LJ , Johnson AG , Jones JR , Shults CL , O'Leary JC , 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. 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.

PubMed ID: 20071522
PMC ID: PMC2830818
Article link: J Neurosci.
Grant support: R00AG031291 NIA NIH HHS , R00 AG031291-03 NIA NIH HHS , R00 AG031291 NIA NIH HHS

Genes referenced: fkbp4 hsp90aa1.1 mapt

External Resources:

Auluck, 2002, Pubmed[+]

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