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Identification and localization of a skeletal muscle secrotonin 5-HT2A receptor coupled to the Jak/STAT pathway.

The neurotransmitter serotonin mediates a wide variety of peripheral and central physiological effects through the binding to multiple receptor subtypes (Wilkinson, L. O., and Dourish, C. T. (1991) in Serotonin Receptor Subtypes: Basic and Clinical Aspects (Peroutka, S. J., ed) Vol. 15, pp.147-210, Wiley-Liss, New York). Among them, serotonin 5-HT2A receptors are known to activate the phospholipase C-beta second messenger pathway (Peroutka, S. J. (1995) Trends Neurosci. 18, 68-69). We identified and localized in rat skeletal muscle myoblasts a functional serotonin 5-HT2A receptor. This receptor was detected on the plasma membrane, in myoblasts, and at the level of T-tubules in contracting myotubes. Binding of serotonin to its receptor increases the expression of genes involved in myogenic differentiation. Unexpectedly, the 5-HT2A receptor is able to activate another signaling pathway; it triggers a rapid and transient tyrosine phosphorylation of Jak2 kinase in response to serotonin. Jak2 auto-phosphorylation is followed by the tyrosine phosphorylation of STAT3 (signal transducers and activators of transcription) and its translocation into the nucleus. We also find that the 5-HT2A receptor and STAT3 co-precipitate with Jak2, indicating that they are physically associated. We conclude that the serotonin 5-HT2A receptor identified in skeletal muscle myoblasts is able to activate the intracellular phosphorylation pathway used by cytokines. The presence of serotonin receptors in T-tubules suggests a role for serotonin in excitation-contraction coupling and (or) an effect in skeletal muscle fiber repairing.

Pubmed ID: 9169451


  • Guillet-Deniau I
  • Burnol AF
  • Girard J


The Journal of biological chemistry

Publication Data

June 6, 1997

Associated Grants


Mesh Terms

  • Animals
  • Base Sequence
  • Cell Membrane
  • Cells, Cultured
  • DNA-Binding Proteins
  • Fetus
  • Glucose Transporter Type 1
  • Glucose Transporter Type 2
  • Janus Kinase 2
  • Molecular Sequence Data
  • Monosaccharide Transport Proteins
  • Muscle, Skeletal
  • Myogenin
  • Phosphorylation
  • Polymerase Chain Reaction
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Rats
  • Receptor, Serotonin, 5-HT2A
  • Receptors, Serotonin
  • STAT3 Transcription Factor
  • Serotonin
  • Signal Transduction
  • Trans-Activators
  • Transcription, Genetic