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Altered G Protein‐Coupling Functions of RNA Editing Isoform and Splicing Variant Serotonin 2C Receptors
Author(s) -
Wang Qingde,
O'Brien Peter J.,
Chen ChunXia,
Cho DanSung C.,
Murray John M.,
Nishikura Kazuko
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.741290.x
Subject(s) - rna editing , gene isoform , biology , rna splicing , receptor , alternative splicing , rna , microbiology and biotechnology , agonist , biochemistry , gene
Different isoforms of serotonin subtype 2C receptor (5‐HT 2C R) with altered G protein‐coupling efficacy are generated by RNA editing, which converts genomically encoded adenosine residues into inosines. In combination, editing of five sites all located within the second intracellular loop region of 5‐HT 2C R mRNA changes the gene‐encoded Ile, Asn, and Ile at positions 156, 158, and 160, respectively. We analyzed the G protien‐coupling functions of previously unreported editing isoform receptors. An ~13‐fold reduction in the agonist potency for G protein‐coupling stimulation as well as a significantly reduced basal level activity was observed with the thalamus‐specific isoform carrying Ile 156 , Gly 158 , and Val 160 (5‐HT 2C R‐IGV). In contrast, the agonist was four‐ to five‐fold less potent with 5‐HT 2C R‐MSV and ‐IDV, detected in the amygdala and choroid plexus, respectively, indicating a dominant role for the amino acid residue at position 158 in receptor functions. We also identified a splicing variant receptor with a truncated C terminus that displayed no ligand binding capacity or G protein‐coupling activity. Examination of the alternatively spliced RNA encoding this truncated receptor suggests that editing of this variant RNA occurs after completion of splicing, resulting in complete editing at all five sites.