5-HT7 receptor is coupled to G alpha subunits of heterotrimeric G12-protein to regulate gene transcription and neuronal morphology.
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.
Kvachnina
Elena
E
Abteilung Neurologie und Sinnesphysiologie, Physiologisches Institut, Universität Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
Liu
Guoquan
G
Dityatev
Alexander
A
Renner
Ute
U
Dumuis
Aline
A
Richter
Diethelm W
DW
Dityateva
Galina
G
Schachner
Melitta
M
Voyno-Yasenetskaya
Tatyana A
TA
Ponimaskin
Evgeni G
EG
D000818:Animals; D002478:Cells, Cultured; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
D043562:Receptors, G-Protein-Coupled; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C104425:serotonin 7 receptor; D012701:Serotonin; D044365:GTP-Binding Protein alpha Subunits, G12-G13