The Hsp90 Cochaperone, FKBP51, Increases Tau Stability and Polymerizes Microtubules

• DOI: 10.1523/jneurosci.4815-09.2010
• Publication Date: 2010-01-13T18:34:52Z
• Authors: Umesh K. Jinwal; John Koren; Sergiy I. Borysov; Andreas B. Schmid; Jose F. Abisambra; Laura J. Blair; Amelia G. Johnson; Jeffrey R. Jones; Cody L. Shults; John C. O'Leary; Ying Jin; Johannes Buchner; Marc B. Cox; Chad A. Dickey
• Keywords: Tetratricopeptide; Chaperone (clinical); Tau protein

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