RNA editing of the serotonin 2C receptor and expression of Galpha(q) protein: genetic mouse models do not support a role for regulation or compensation.
The serotonin 2C (5-HT(2C)) receptor undergoes RNA editing at five bases in a region of the pre-mRNA encoding the second intracellular loop, generating many unique 5-HT(2C) receptor isoforms. Mechanisms regulating in vivo expression of different edited 5-HT(2C) receptor isoforms are poorly understood, as are the adaptive consequences of variation in editing profiles. Recent findings suggest a putative relationship between expression levels of Galpha(q/11) protein and the degree of editing of 5-HT(2C) receptor transcripts. To elucidate the potential regulatory or adaptive role of Galpha(q/11) protein levels, we quantified editing of 5-HT(2C) receptor RNA transcripts in Galpha(q) null mice and protein levels of Galpha(q) and Galpha(11) in transgenic male mice solely expressing either the non-edited (INI) or the fully edited (VGV) isoforms of the 5-HT(2C) receptor. Pyrosequencing of RNA isolated from amygdaloid cortex in Galpha(q) null and wild-type mice revealed no significant differences in 5-HT(2C) receptor mRNA editing profiles. Cortical tissue from INI/y, VGV/y, and wild-type mice was assayed for expression of Galpha(q) and Galpha(11) subunits by Western blotting. No differences in signal density between wild-type and INI/y or VGV/y groups were found, indicating equivalent levels of Galpha(q) and Galpha(11) protein. Together, these data do not support a causal or compensatory relationship between 5-HT(2C) receptor RNA editing and G(q) protein levels.
Canal
Clinton E
CE
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Mahautmr
Kontip C
KC
Cao
Chike
C
Sanders-Bush
Elaine
E
Airey
David C
DC
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression / Q000235:genetics*; D055879:Gene Knock-In Techniques / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D017393:RNA Editing / Q000235:genetics*; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*
D020033:Protein Isoforms; D044405:Receptor, Serotonin, 5-HT2C; D012313:RNA; D043802:GTP-Binding Protein alpha Subunits, Gq-G11