The calpain-calpastatin system and protein degradation in fusing myoblasts

Sivia Barnoy, Tova Glaser, Nechama S. Kosower*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Calpain (Ca2+-activated cysteine protease) induced proteolysis has been suggested to play a role in myoblast fusion. We previously found that calpastatin (the endogenous inhibitor of calpain) diminishes markedly in myoblasts during myoblast differentiation just prior to the start of fusion, allowing Ca2+-induced calpain activation at that stage. Here, we show that a limited degradation of some proteins occurs within the myoblasts undergoing fusion, but not in proliferating myoblasts. The protein degradation is observed at the stage when calpastatin is low. Protein degradation within the myoblasts and myoblast fusion are inhibited by EGTA, by the cysteine protease inhibitors calpeptin and E-64d and by calpastatin. The degradation appears to be selective for certain myoblast proteins. Integrin β1 subunit, talin and β-tropomyosin are degraded in the fusing myoblasts, whereas α-actinin, β-tubulin and α-tropomyosin are not. A similar pattern of degradation is observed in lysates of proliferating myoblasts when Ca2+ and excess calpain are added, a degradation that is inhibited by calpastatin. The results support the notion that degradation of certain proteins is required for myoblast fusion and that calpain participates in the fusion-associated protein degradation. Participation of calpain is made possible by a change in calpain/calpastatin ratio, i.e., by a diminution in calpastatin level from a high level in the proliferating myoblasts to a low level in the differentiating myoblasts. Degradation of certain proteins, known to be responsible for the stability of the membrane-skeleton organization and for the interaction of the cell with the extracellular matrix, would allow destabilization of the membrane and the creation of membrane fusion-potent regions.

Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1402
Issue number1
DOIs
StatePublished - 12 Mar 1998

Keywords

  • Calpain
  • Calpastatin
  • Myoblast fusion
  • Myoblast protein degradation

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