RGD Reference Report - ATP regulates the differentiation of mammalian skeletal muscle by activation of a P2X5 receptor on satellite cells. - Rat Genome Database

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ATP regulates the differentiation of mammalian skeletal muscle by activation of a P2X5 receptor on satellite cells.

Authors: Ryten, M  Dunn, PM  Neary, JT  Burnstock, G 
Citation: Ryten M, etal., J Cell Biol 2002 Jul 22;158(2):345-55.
RGD ID: 729229
Pubmed: PMID:12135987   (View Abstract at PubMed)
PMCID: PMC2173112   (View Article at PubMed Central)
DOI: DOI:10.1083/jcb.200202025   (Journal Full-text)

ATP is well known for its role as an intracellular energy source. However, there is increasing awareness of its role as an extracellular messenger molecule (Burnstock, 1997). Although evidence for the presence of receptors for extracellular ATP on skeletal myoblasts was first published in 1983 (Kolb and Wakelam), their physiological function has remained unclear. In this paper we used primary cultures of rat skeletal muscle satellite cells to investigate the role of purinergic signaling in muscle formation. Using immunocytochemistry, RT-PCR, and electrophysiology, we demonstrate that the ionotropic P2X5 receptor is present on satellite cells and that activation of a P2X receptor inhibits proliferation, stimulates expression of markers of muscle cell differentiation, including myogenin, p21, and myosin heavy chain, and increases the rate of myotube formation. Furthermore, we demonstrate that ATP application results in a significant and rapid increase in the phosphorylation of MAPKs, particularly p38, and that inhibition of p38 activity can prevent the effect of ATP on cell number. These results not only demonstrate the existence of a novel regulator of skeletal muscle differentiation, namely ATP, but also a new role for ionotropic P2X receptors in the control of cell fate.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
monoatomic cation transport  TAS 729229 RGD 
regulation of skeletal muscle tissue regeneration  IMP 729229 RGD 
skeletal muscle tissue growth  TAS 729229 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
extracellularly ATP-gated monoatomic cation channel activity  IDA 729229 RGD 

Objects Annotated

Genes (Rattus norvegicus)
P2rx5  (purinergic receptor P2X 5)


Additional Information