Identification and Localization of a Skeletal Muscle Secrotonin 5-HT2AReceptor Coupled to the Jak/STAT Pathway

Isabelle Guillet-Deniau, Anne-Françoise Burnol, Jean Girard
1997 Journal of Biological Chemistry  
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
more » ... 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.
doi:10.1074/jbc.272.23.14825 pmid:9169451 fatcat:76zjyifen5dklagpzwnqet7yki