α-Syntrophin alleviates ER stress to maintain protein homeostasis during myoblast differentiation

FEBS Lett. 2021 Jun;595(12):1656-1670. doi: 10.1002/1873-3468.14088. Epub 2021 Apr 22.

Abstract

We have previously shown evidence that α-syntrophin plays an important role in myoblast differentiation. In this study, we focused on abnormal myotube formation of the α-syntrophin knockdown C2 cell line (SNKD). The overall amount of intracellular protein and muscle-specific proteins in SNKD cells were significantly lower than those in the control. Akt-mTOR signaling, an important pathway for protein synthesis and muscle hypertrophy, was downregulated. In addition, the levels of endoplasmic reticulum (ER) stress markers increased in SNKD cells. The decrease in intracellular protein synthesis and reduction in the myotube diameter in SNKD cells were restored by 4-phenylbutyric acid, a chemical chaperone, or overexpression of α-syntrophin. These results suggest a novel role for α-syntrophin in protein homeostasis during myoblast differentiation.

Keywords: endoplasmic reticulum stress; muscle differentiation; protein homeostasis; protein synthesis; α-syntrophin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Differentiation*
  • Cell Line
  • Endoplasmic Reticulum Stress*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism*
  • Myoblasts / metabolism*
  • Proteostasis*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Calcium-Binding Proteins
  • Membrane Proteins
  • Muscle Proteins
  • syntrophin alpha1
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases