The calcineurin pathway links hyperpolarization (Kir2.1)-induced Ca2+ signals to human myoblast differentiation and fusion

Autor: Charles R. Bader, Anne Béguet, Laurent Bernheim, Stéphane König
Rok vydání: 2006
Předmět:
Mef2
Myogenic Regulatory Factors/metabolism
Calcineurin Pathway
Cellular differentiation
Biology
p38 Mitogen-Activated Protein Kinases
Cell Fusion
Myoblasts
Phosphatidylinositol 3-Kinases
Myogenin/metabolism
Humans
Calcium Signaling
Potassium Channels
Inwardly Rectifying
Molecular Biology
CAMK
Myogenin
PI3K/AKT/mTOR pathway
MEF2 Transcription Factors
Cell Membrane/metabolism
Calcineurin
Cell Membrane
Cell Polarity
Cell Differentiation
Hyperpolarization (biology)
musculoskeletal system
ddc:616.8
Cell biology
Biochemistry
Myogenic Regulatory Factors
Calcineurin/ metabolism
Calcium-Calmodulin-Dependent Protein Kinases/metabolism
Potassium Channels
Inwardly Rectifying/ metabolism
P38 Mitogen-Activated Protein Kinases/metabolism
Calcium-Calmodulin-Dependent Protein Kinases
cardiovascular system
Myoblasts/ cytology/metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2
tissues
Developmental Biology
Zdroj: Development, Vol. 133, No 16 (2006) pp. 3107-3114
ISSN: 0950-1991
Popis: 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.
Databáze: OpenAIRE
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