RNA editing of the human serotonin 5-HT2C receptor disrupts transactivation of the small G-protein RhoA.
The human serotonin 5-HT2C receptor undergoes adenosineto-inosine RNA editing at five positions, generating multiple receptor isoforms with altered G-protein coupling properties. In the current study, we demonstrate that RNA editing regulates the pattern of intracellular signaling. The non-edited human 5-HT2C receptor isoform INI activates phospholipase D via the G13 heterotrimer G-protein. We present evidence that transactivation of the small G-protein RhoA is required for phospholipase D activation. In contrast, neither transactivation of RhoA nor phospholipase D activation was detected in cells expressing the fully edited VGV isoform. The ability to activate phospholipase C is also reduced in VGV-expressing cells, but not to the extent found for the phospholipase D signal. We conclude that RNA editing represents a novel mechanism for regulating 5-HT2C receptor signaling to pathways linked to actin cytoskeletal organization and regulated exocytosis.
McGrew
Lori
L
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Price
Raymond D
RD
Hackler
Elizabeth
E
Chang
Mike S S
MS
Sanders-Bush
Elaine
E
D004789:Enzyme Activation; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism; D017393:RNA Editing; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D044405:Receptor, Serotonin, 5-HT2C; D010739:Phospholipase D; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D020559:Monomeric GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein