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

Published in The Journal of biological chemistry. 2009, vol. 284, no. 8, p. 5370-80
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/metabolismCalcium Channels/genetics/metabolismCell Differentiation/physiologyCells, CulturedChild, PreschoolFemaleGene Knockdown TechniquesHumansInfantMaleMembrane Potentials/physiologyMembrane Proteins/genetics/metabolismMyoblasts/metabolismMyogenic Regulatory Factors/genetics/metabolismMyogenin/genetics/metabolismNeoplasm Proteins/genetics/metabolism
PMID: 19088073
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Other version: http://www.jbc.org/content/284/8/5370.long
Research groups Culture Primaire de myoblastes humains (208)
Signaux intracellulaires (210)
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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. 5370-80. doi: 10.1074/jbc.M806726200 https://archive-ouverte.unige.ch/unige:3885

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Deposited on : 2009-10-23

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