Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Cell Rep. 2012 May 31;1(5):557-69. doi: 10.1016/j.celrep.2012.03.014. Epub 2012 May 3.

Mouse skeletal muscle fiber-type-specific macroautophagy and muscle wasting are regulated by a Fyn/STAT3/Vps34 signaling pathway.

Author information

  • 1Department of Medicine, Albert Einstein College of Medicine, Diabetes Research and Training Center, Bronx, NY 10461, USA.

Abstract

Skeletal muscle atrophy induced by aging (sarcopenia), inactivity, and prolonged fasting states (starvation) is predominantly restricted to glycolytic type II muscle fibers and typical spares oxidative type I fibers. However, the mechanisms accounting for muscle fiber-type specificity of atrophy have remained enigmatic. In the current study, although the Fyn tyrosine kinase activated the mTORC1 signaling complex, it also induced marked atrophy of glycolytic fibers with relatively less effect on oxidative muscle fibers. This was due to inhibition of macroautophagy via an mTORC1-independent but STAT3-dependent reduction in Vps34 protein levels and decreased Vps34/p150/Beclin1/Atg14 complex 1. Physiologically, in the fed state endogenous Fyn kinase activity was increased in glycolytic but not oxidative skeletal muscle. In parallel, Y705-STAT3 phosphorylation increased with decreased Vps34 protein levels. Moreover, fed/starved regulation of Y705-STAT3 phosphorylation and Vps34 protein levels was prevented in skeletal muscle of Fyn null mice. These data demonstrate a Fyn/STAT3/Vps34 pathway that is responsible for fiber-type-specific regulation of macroautophagy and skeletal muscle atrophy.

Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

KEYWORDS:

Fyn; LKB1; STAT3; Vps34; autophagy; mTORC1; muscle atrophy

PMID:
22745922
[PubMed - indexed for MEDLINE]
PMCID:
PMC3383827
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk