| First Author | Tanowitz M | Year | 2008 |
| Journal | J Biol Chem | Volume | 283 |
| Issue | 51 | Pages | 35614-21 |
| PubMed ID | 18936093 | Mgi Jnum | J:144555 |
| Mgi Id | MGI:3831214 | Doi | 10.1074/jbc.M806588200 |
| Citation | Tanowitz M, et al. (2008) Alternative splicing determines the post-endocytic sorting fate of G-protein-coupled receptors. J Biol Chem 283(51):35614-21 |
| abstractText | Mu-type opioid receptors are physiologically important G-protein-coupled receptors that are generally thought to recycle after agonist-induced endocytosis. Here we show that several alternatively spliced receptor variants fail to do so efficiently because of splice-mediated removal of an endocytic sorting sequence that is present specifically in the MOR1 variant. All of the recycling-impaired receptor variants were found to undergo proteolytic down-regulation more rapidly than MOR1, irrespective of moderate differences in endocytic rate, indicating that alternative splicing plays a specific role in distinguishing the trafficking itinerary of receptors after endocytosis. The recycling-impaired MOR1B variant was similar to MOR1 in its ability to mediate opioid-dependent inhibition of adenylyl cyclase, and to undergo opioid-induced desensitization in intact cells. Functional recovery (resensitization) of MOR1B-mediated cellular responsiveness after opioid removal, however, was significantly impaired (4-fold reduction in rate) compared with MOR1. To our knowledge the present results are the first to establish a role of alternative RNA processing in specifying the post-endocytic sorting of G-protein-coupled receptors between divergent and functionally distinct membrane pathways. |
