Neuropathy-causing mutations in HSPB1 impair autophagy by disturbing the formation of SQSTM1/p62 bodies.

ABSTRACT: HSPB1 (heat shock protein family B [small] member 1) is a ubiquitously expressed molecular chaperone. Most mutations in HSPB1 cause axonal Charcot-Marie-Tooth neuropathy and/or distal hereditary motor neuropathy. In this study we show that mutations in HSPB1 lead to impairment of macroautophagic/autophagic flux. In HSPB1 knockout cells, we demonstrate that HSPB1 is necessary for autophagosome formation, which was rescued upon re-expression of HSPB1. Employing a label-free LC-MS/MS analysis on the various HSPB1 variants (wild type and mutants), we identified autophagy-specific interactors. We reveal that the wild-type HSPB1 protein binds to the autophagy receptor SQSTM1/p62 and that the PB1 domain of SQSTM1 is essential for this interaction. Mutations in HSPB1 lead to a decrease in the form

SUBMITTER: Haidar M 

PROVIDER: S-EPMC6526868 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature