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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
51
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pubmed:dateCreated |
2008-12-16
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pubmed: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.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-10215631,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-10419560,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-10499588,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-10753919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-10851176,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-10854754,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-11102461,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-11166849,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-11208108,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-11359768,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-11560936,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-12401797,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-12764121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-12939277,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-14686893,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-15040445,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-15229652,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-15464145,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-15464147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-16611829,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-16896947,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-18031739,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-18068348,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-18076994,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-18184106,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-269396,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-7532594,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-7957926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-8114680,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-8385579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-8786444,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-8893006,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-9277131,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-9327928,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-942051,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-9495801,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-9585136,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-9593704,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18936093-9707575
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
283
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
35614-21
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pubmed:dateRevised |
2010-9-21
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pubmed:meshHeading |
pubmed-meshheading:18936093-Adenylate Cyclase,
pubmed-meshheading:18936093-Alternative Splicing,
pubmed-meshheading:18936093-Cell Line,
pubmed-meshheading:18936093-Cell Membrane,
pubmed-meshheading:18936093-Down-Regulation,
pubmed-meshheading:18936093-Endocytosis,
pubmed-meshheading:18936093-Humans,
pubmed-meshheading:18936093-Protein Isoforms,
pubmed-meshheading:18936093-Protein Transport,
pubmed-meshheading:18936093-Receptors, Opioid, mu
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pubmed:year |
2008
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pubmed:articleTitle |
Alternative splicing determines the post-endocytic sorting fate of G-protein-coupled receptors.
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pubmed:affiliation |
Department of Psychiatry, University of California, San Francisco, California 94158-2140, USA
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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