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New serotonergic pathways regulating gene transcription and neuronal morphology
Author(s) -
Ponimaskin Evgeni G.,
Kwachnina Elena,
Renner Utte,
Dityatev Alexander,
Schachner Melitta,
VoynoYasenetskaya Tatyana
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a933-b
Subject(s) - heterotrimeric g protein , rhoa , microbiology and biotechnology , neurite , neurotransmitter receptor , serotonergic , cdc42 , biology , neurotransmission , neuroscience , chemistry , signal transduction , receptor , g protein , serotonin , biochemistry , in vitro
Serotonin (5‐hydroxytryptamine or 5‐HT) is an important neurotransmitter involved in a wide range of central and peripheral physiological functions. A number of different G‐protein coupled 5‐HT receptors are known to sensitively modify different neuronal networks by their specific action on synaptic transmission and postsynaptic excitability. Here we show for the first time that the 5‐HT4 receptor is coupled not only to the heterotrimeric Gs, but also to G13 protein. Activation of this signaling pathway results in RhoA‐mediated modulation of gene transcription and in reorganization of the actin cytoskeleton. We also demonstrated that serotonin receptor 5‐HT7 can activate heterotrimeric G12 protein, leading to the selective activation of small GTPases RhoA and Cdc42. Agonist‐dependent activation of the 5‐HT7 receptor induced pronounced filopodia formation via a Cdc42‐mediated pathway paralleled by RhoA‐dependent cell rounding. Analysis of mouse hippocampal neurons demonstrated that activation of the endogenous 5‐HT7 receptors significantly increased neurite length, whereas stimulation of the endogenous 5‐HT4 receptors lead to a pronounced decrease in the length and number of neurites. These data demonstrate distinct roles for the 5‐HT7R/G12 and 5‐HT4R/G13 signaling pathways in the neurite outgrowth/retraction, and also suggest that serotonin plays a prominent role in regulating the neuronal cyto‐architecture in addition to its classical role as neurotransmitter.