Isolating and characterizing three alternatively spliced mu opioid receptor variants: MMOR-1A, mMOR-1O, and mMOR-1P Journal Article
| Authors: | Xu, J.; Xu, M.; Bolan, E.; Gilbert, A. K.; Pasternak, G. W.; Pan, Y. X. |
| Article Title: | Isolating and characterizing three alternatively spliced mu opioid receptor variants: MMOR-1A, mMOR-1O, and mMOR-1P |
| Abstract: | Extensive alternative pre-mRNA splicing of the mu opioid receptor gene, OPRM1, has demonstrated an array of splice variants in mice, rats and humans. Three classes of splice variants have been identified: full-length seven transmembrane (TM) domain variants with C-terminal splicing, truncated 6TM variants and single TM variants. The current studies isolates and characterizes an additional three full-length C-terminal splice variants generated from the mouse OPRM1 gene: mMOR-1A, mMOR-1O, and mMOR-1P. Using RT-qPCR, we demonstrated differential expression of these variants' mRNAs among selected brain regions, supporting region-specific alternative splicing. When expressed in Chinese Hamster Ovary cells, all the variants displayed high mu binding affinity and selectivity with subtle differences in the affinities toward some agonists. [35S]γGTP binding assays revealed marked differences in agonist-induced G protein activation in both potency and efficacy among the variants. Together with the previous studies of mu agonist-induced phosphorylation and internalization in several carboxyl terminal splice variants, the current studies further suggest the existence of biased signaling of various agonists within each individual variant and/or among different variants. © 2013 Wiley Periodicals, Inc. |
| Keywords: | alternative splicing; morphine; oprm1; gpcr; g-protein coupled receptor; biased agonism; biased signaling; opioid peptide |
| Journal Title: | Synapse |
| Volume: | 68 |
| Issue: | 4 |
| ISSN: | 0887-4476 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2014-04-01 |
| Start Page: | 144 |
| End Page: | 152 |
| Language: | English |
| DOI: | 10.1002/syn.21727 |
| PROVIDER: | scopus |
| PMCID: | PMC3926657 |
| PUBMED: | 24375714 |
| DOI/URL: | |
| Notes: | Export Date: 3 March 2014 -- CODEN: SYNAE -- Source: Scopus |
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