A signaling hub of insulin receptor, dystrophin glycoprotein complex and plakoglobin regulates muscle size.

ABSTRACT: Signaling through the insulin receptor governs central physiological functions related to cell growth and metabolism. Here we show by tandem native protein complex purification approach and super-resolution STED microscopy that insulin receptor activity requires association with the fundamental structural module in muscle, the dystrophin glycoprotein complex (DGC), and the desmosomal component plakoglobin (γ-catenin). The integrity of this high-molecular-mass assembly renders skeletal muscle susceptibility to insulin, because DGC-insulin receptor dissociation by plakoglobin downregulation reduces insulin signaling and causes atrophy. Furthermore, low insulin receptor activity in muscles from transgenic or fasted mice decreases plakoglobin-DGC-insulin receptor content on the plasma membrane

SUBMITTER: Eid Mutlak Y 

PROVIDER: S-EPMC7070008 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature