Journal of Biological Chemistry
Volume 285, Issue 17, 23 April 2010, Pages 12670-12683
Journal home page for Journal of Biological Chemistry

Cell Biology
Down-regulation of MyoD by Calpain 3 Promotes Generation of Reserve Cells in C2C12 Myoblasts*

https://doi.org/10.1074/jbc.M109.063966Get rights and content
Under a Creative Commons license
open access

Calpain 3 is a calcium-dependent cysteine protease that is primarily expressed in skeletal muscle and is implicated in limb girdle muscular dystrophy type 2A. To date, its best characterized function is located within the sarcomere, but this protease is found in other cellular compartments, which suggests that it exerts multiple roles. Here, we present evidence that calpain 3 is involved in the myogenic differentiation process. In the course of in vitro culture of myoblasts to fully differentiated myotubes, a population of quiescent undifferentiated “reserve cells” are maintained. These reserve cells are closely related to satellite cells responsible for adult muscle regeneration. In the present work, we observe that reserve cells express higher levels of endogenous Capn3 mRNA than proliferating myoblasts. We show that calpain 3 participates in the establishment of the pool of reserve cells by decreasing the transcriptional activity of the key myogenic regulator MyoD via proteolysis independently of the ubiquitin-proteasome degradation pathway. Our results identify calpain 3 as a potential new player in the muscular regeneration process by promoting renewal of the satellite cell compartment.

Cell/Differentiation
Development Differentiation/Muscle
Diseases/Muscular Dystrophy
Protease/Calpain
Protein/Degradation
Stem Cells
Transcription/Helix-loop-helix
Transcription/Tissue-specific Factors

Cited by (0)

*

This work was supported by grants from the Institut National de la Recherche Agronomique, the Region Aquitaine, and the “Association Française contre les Myopathies.”

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.

1

Present address: Dept. of Biological Structure, School of Medicine, University of Washington, Seattle, WA 98195.

2

Present address: Laboratoire UPRES EA (Unité Propre de Recherche de l'Enseignement Supérieur, Equipe d'Accueil) 27-10 Radiosensibilité des Tumeurs et Tissus Sains, Institut Gustave Roussy, 39 Rue Camille Desmoulins, F-94805 Villejuif, France.

3

Present address: Unité de Recherche en Génétique Humaine Centre Hospitalier de l'Université Laval 2705, Boul. Laurier, Québec, Québec RC-9300, Canada.