Class B J-domain proteins mediate Tau disaggregation.
A, Tau fibrils made up from 1N3R or 1N4R were treated with HSC70, HSPA4, and different HSP40 class A and class B J-domain proteins, respectively. Subsequently, S and P fractions were separated by centrifugation and Tau levels were analyzed by Western blotting. Asterisks indicate successful disaggregation reactions. B, densitometric quantification of 1N3R Tau levels in S fractions compared with the total (S + P) as shown in panel A. n = 3, mean ± S.D. One-way ANOVA with Bonferroni's multiple-comparison test was used. Only significances to the −Chaperone +ATP condition are indicated. ***, p ≤ 0.001. C, densitometric quantification of 1N4R Tau levels in S fractions compared with the total (S + P) as shown in panel A. n = 3, mean ± S.D. One-way ANOVA with Bonferroni's multiple comparison test was used. Only significances to the –Chaperone (−Chap) +ATP condition are indicated. ***, p ≤ 0.001.