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Volume 272, Number 23, Issue of June 6, 1997 pp. 14825-14829
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Identification and Localization of a Skeletal Muscle Secrotonin 5-HT_2A Receptor Coupled to the Jak/STAT Pathway

(Received for publication, October 21, 1996, and in revised form, March 17, 1997)

From the Centre de Recherches sur l'Endocrinologie Moléculaire et le Développement, CNRS, UPR 1511, 9, rue Jules Hetzel, 92 190 Meudon, France

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-HT_2A receptors are known to activate the phospholipase C- 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-HT_2A 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-HT_2A 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-HT_2A receptor and STAT3 co-precipitate with Jak2, indicating that they are physically associated. We conclude that the serotonin 5-HT_2A 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.

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