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Scientific article
English

STIM1- and Orai1-dependent store-operated calcium entry regulates human myoblast differentiation

Contributors

Darbellay, Basile; Arnaudeau, Serge; Konig, Stéphane; Jousset, Hélène; Bader, Charles; Demaurex, Nicolas; Bernheim, Laurent

Published in

The Journal of biological chemistry, vol. 284, no. 8, p. 5370-5380

Publication date

2009

Abstract

Our previous work on human myoblasts suggested that a hyperpolarization followed by a rise in [Ca(2+)](in) involving store-operated Ca(2+) entry (SOCE) channels induced myoblast differentiation. Advances in the understanding of the SOCE pathway led us to examine more precisely its role in post-natal human myoblast differentiation. We found that SOCE orchestrated by STIM1, the endoplasmic reticulum Ca(2+) sensor activating Orai Ca(2+) channels, is crucial. Silencing STIM1, Orai1, or Orai3 reduced SOCE amplitude and myoblast differentiation, whereas Orai2 knockdown had no effect. Conversely, overexpression of STIM1 with Orai1 increased SOCE and accelerated myoblast differentiation. STIM1 or Orai1 silencing decreased resting [Ca(2+)](in) and intracellular Ca(2+) store content, but correction of these parameters did not rescue myoblast differentiation. Remarkably, SOCE amplitude correlated linearly with the expression of two early markers of myoblast differentiation, MEF2 and myogenin, regardless of the STIM or Orai isoform that was silenced. Unexpectedly, we found that the hyperpolarization also depends on SOCE, placing SOCE upstream of K(+) channel activation in the signaling cascade that controls myoblast differentiation. These findings indicate that STIM1 and Orai1 are key molecules for the induction of human myoblast differentiation.

Keywords

  • Calcium/metabolism
  • Calcium Channels/genetics/metabolism
  • Cell Differentiation/physiology
  • Cells, Cultured
  • Child, Preschool
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Infant
  • Male
  • Membrane Potentials/physiology
  • Membrane Proteins/genetics/metabolism
  • Myoblasts/metabolism
  • Myogenic Regulatory Factors/genetics/metabolism
  • Myogenin/genetics/metabolism
  • Neoplasm Proteins/genetics/metabolism

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

DARBELLAY, Basile et al. STIM1- and Orai1-dependent store-operated calcium entry regulates human myoblast differentiation. In: The Journal of biological chemistry, 2009, vol. 284, n° 8, p. 5370–5380. doi: 10.1074/jbc.M806726200

Main files (1)

Article (Accepted version)

Identifiers

Additional URL for this publication

http://www.jbc.org/content/284/8/5370.long

Journal ISSN

0021-9258
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Technical informations

Creation

21/10/2009 17:00:00

First validation

21/10/2009 17:00:00

Update

14/03/2023 15:16:50

Status update

14/03/2023 15:16:50

Last indexation

29/10/2024 12:29:00
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