5-HT7 receptor is coupled to G alpha subunits of heterotrimeric G12-protein to regulate gene transcription and neuronal morphology

• Published in: The Journal of neuroscience Vol. 25; no. 34; pp. 7821 - 7830
• Main Authors: Kvachnina, Elena, Liu, Guoquan, Dityatev, Alexander, Renner, Ute, Dumuis, Aline, Richter, Diethelm W, Dityateva, Galina, Schachner, Melitta, Voyno-Yasenetskaya, Tatyana A, Ponimaskin, Evgeni G
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 24.08.2005
• Subjects: Animals; Biochemistry, Molecular Biology; Cells, Cultured; Comparative Study; Development/Plasticity/Repair; GTP-Binding Protein alpha Subunits, G12-G13; GTP-Binding Protein alpha Subunits, G12-G13 - genetics; GTP-Binding Protein alpha Subunits, G12-G13 - metabolism; Life Sciences; Mice; Neurites; Neurites - physiology; Neurons; Neurons - cytology; Neurons - metabolism; NIH 3T3 Cells; Receptors, G-Protein-Coupled; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Receptors, Serotonin; Receptors, Serotonin - genetics; Receptors, Serotonin - metabolism; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Serotonin - physiology; Serotonin Antagonists - pharmacology; Signal Transduction - physiology; Transcription, Genetic - physiology
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.1790-05.2005

The neurotransmitter serotonin (5-HT) plays an important role in the regulation of multiple events in the CNS. We demonstrated recently a coupling between the 5-HT4 receptor and the heterotrimeric G13-protein resulting in RhoA-dependent neurite retraction and cell rounding (Ponimaskin et al., 2002). In the present study, we identified G12 as an additional G-protein that can be activated by another member of serotonin receptors, the 5-HT7 receptor. Expression of 5-HT7 receptor induced constitutive and agonist-dependent activation of a serum response element-mediated gene transcription through G12-mediated activation of small GTPases. In NIH3T3 cells, activation of the 5-HT7 receptor induced filopodia formation via a Cdc42-mediated pathway correlating with RhoA-dependent cell rounding. In mouse hippocampal neurons, activation of the endogenous 5-HT7 receptors significantly increased neurite length, whereas stimulation of 5-HT4 receptors led to a decrease in the length and number of neurites. These data demonstrate distinct roles for 5-HT7R/G12 and 5-HT4R/G13 signaling pathways in neurite outgrowth and retraction, suggesting that serotonin plays a prominent role in regulating the neuronal cytoarchitecture in addition to its classical role as neurotransmitter.