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The calcineurin pathway links hyperpolarization (Kir2.1)-induced Ca2+ signals to human myoblast differentiation and fusion.
- Source :
-
Development (Cambridge, England) [Development] 2006 Aug; Vol. 133 (16), pp. 3107-14. Date of Electronic Publication: 2006 Jul 10. - Publication Year :
- 2006
-
Abstract
- In human myoblasts triggered to differentiate, a hyperpolarization, resulting from K+ channel (Kir2.1) activation, allows the generation of an intracellular Ca2+ signal. This signal induces an increase in expression/activity of two key transcription factors of the differentiation process, myogenin and MEF2. Blocking hyperpolarization inhibits myoblast differentiation. The link between hyperpolarization-induced Ca2+ signals and the four main regulatory pathways involved in myoblast differentiation was the object of this study. Of the calcineurin, p38-MAPK, PI3K and CaMK pathways, only the calcineurin pathway was inhibited when Kir2.1-linked hyperpolarization was blocked. The CaMK pathway, although Ca2+ dependent, is unaffected by changes in membrane potential or block of Kir2.1 channels. Concerning the p38-MAPK and PI3K pathways, their activity is present already in proliferating myoblasts and they are unaffected by hyperpolarization or Kir2.1 channel block. We conclude that the Kir2.1-induced hyperpolarization triggers human myoblast differentiation via the activation of the calcineurin pathway, which, in turn, induces expression/activity of myogenin and MEF2.
- Subjects :
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases metabolism
Cell Fusion
Cell Membrane metabolism
Cell Polarity
Humans
MEF2 Transcription Factors
Myoblasts metabolism
Myogenic Regulatory Factors metabolism
Myogenin metabolism
Phosphatidylinositol 3-Kinases metabolism
p38 Mitogen-Activated Protein Kinases metabolism
Calcineurin metabolism
Calcium Signaling
Cell Differentiation
Myoblasts cytology
Potassium Channels, Inwardly Rectifying metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0950-1991
- Volume :
- 133
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Development (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 16831831
- Full Text :
- https://doi.org/10.1242/dev.02479