Down-regulation of MyoD by calpain 3 promotes generation of reserve cells in C2C12 myoblasts.
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.
Université Bordeaux 1, Unité Protéolyse Croissance et Développement Musculaire, Institut National de la Recherche Agronomique, USC 2009, Avenue des Facultés, F-33405 Talence, France.
Pascal
P
Stuelsatz
Frédéric
F
Pouzoulet
Yann
Y
Lamarre
Elise
E
Dargelos
Sylvie
S
Poussard
Serge
S
Leibovitch
Patrick
P
Cottin
Philippe
P
Veschambre
D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000235:genetics / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism
D009124:Muscle Proteins; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D025801:Ubiquitin; C105884:CAPN3 protein, human; D002154:Calpain; D046988:Proteasome Endopeptidase Complex