STIM1- and Orai1-dependent store-operated calcium entry regulates human myoblast differentiation
| Autor: | Basile Darbellay, Hélène Jousset, Nicolas Demaurex, Serge Arnaudeau, Charles R. Bader, Stéphane König, Laurent Bernheim |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
ORAI1 Protein Biochemistry Membrane Potentials Myoblasts 0302 clinical medicine Myocyte Myogenin/genetics/metabolism Cells Cultured 0303 health sciences ORAI1 STIM1 Cell Differentiation Hyperpolarization (biology) Membrane Proteins/genetics/metabolism musculoskeletal system Store-operated calcium entry Cell biology Neoplasm Proteins Myogenic Regulatory Factors Membrane Potentials/physiology Child Preschool Gene Knockdown Techniques Female Myogenin tissues Mef2 Calcium/metabolism Biology Neoplasm Proteins/genetics/metabolism Myogenic Regulatory Factors/genetics/metabolism 03 medical and health sciences Cell Differentiation/physiology Humans Stromal Interaction Molecule 1 ddc:612 Molecular Biology 030304 developmental biology Calcium Channels/genetics/metabolism Endoplasmic reticulum Myoblasts/metabolism Infant Membrane Proteins Cell Biology ddc:616.8 Immunology Calcium Calcium Channels 030217 neurology & neurosurgery |
| Zdroj: | The Journal of biological chemistry Journal of Biological Chemistry, Vol. 284, No 8 (2009) pp. 5370-80 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.M806726200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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