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PMID:20139084

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Citation

Stuelsatz, P, Pouzoulet, F, Lamarre, Y, Dargelos, E, Poussard, S, Leibovitch, S, Cottin, P and Veschambre, P (2010) Down-regulation of MyoD by calpain 3 promotes generation of reserve cells in C2C12 myoblasts. J. Biol. Chem. 285:12670-83

Abstract

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.

Links

PubMed PMC2857084 Online version:10.1074/jbc.M109.063966

Keywords

Calpain/genetics; Calpain/metabolism; Cell Differentiation; Cell Line; Down-Regulation; Humans; Muscle Development; Muscle Fibers, Skeletal/metabolism; Muscle Proteins/genetics; Muscle Proteins/metabolism; Muscular Dystrophies/genetics; Muscular Dystrophies/metabolism; MyoD Protein/genetics; MyoD Protein/metabolism; Myoblasts/metabolism; Proteasome Endopeptidase Complex/genetics; Proteasome Endopeptidase Complex/metabolism; Regeneration/genetics; Satellite Cells, Skeletal Muscle/metabolism; Transcription, Genetic/genetics; Ubiquitin/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:MYOD1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CAN3

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:CAN3

involved_in

GO:0014718: positive regulation of satellite cell activation involved in skeletal muscle regeneration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CAN3

involved_in

GO:0045892: negative regulation of transcription, DNA-templated

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P10085)

Seeded From UniProt

complete

MOUSE:CAN3

involved_in

GO:0045862: positive regulation of proteolysis

ECO:0000314: direct assay evidence used in manual assertion

P

  • has_input:(UniProtKB:P10085)

Seeded From UniProt

complete

MOUSE:CAN3

involved_in

GO:0045661: regulation of myoblast differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:CAN3

involved_in

GO:0070315: G1 to G0 transition involved in cell differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:MYOD1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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