GSK3-β promotes calpain-1-mediated desmin filament depolymerization and myofibril loss in atrophy.

ABSTRACT: Myofibril breakdown is a fundamental cause of muscle wasting and inevitable sequel of aging and disease. We demonstrated that myofibril loss requires depolymerization of the desmin cytoskeleton, which is activated by phosphorylation. Here, we developed a mass spectrometry-based kinase-trap assay and identified glycogen synthase kinase 3-β (GSK3-β) as responsible for desmin phosphorylation. GSK3-β inhibition in mice prevented desmin phosphorylation and depolymerization and blocked atrophy upon fasting or denervation. Desmin was phosphorylated by GSK3-β 3 d after denervation, but depolymerized only 4 d later when cytosolic Ca²⁺ levels rose. Mass spectrometry analysis identified GSK3-β and the Ca²⁺-specific protease, calpain-1, bound to desmin and catalyzing its disassem

SUBMITTER: Aweida D 

PROVIDER: S-EPMC6168250 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature