RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking.
Receptor internalization from the cell surface occurs through several mechanisms. Some of these mechanisms, such as clathrin coated pits, are well understood. The M(2) muscarinic acetylcholine receptor undergoes internalization via a poorly-defined clathrin-independent mechanism. We used isotope cod...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-10-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2958127?pdf=render |
| _version_ | 1818021333173272576 |
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| author | Cindy L Reiner Jennifer S McCullar Rebecca L Kow Joshua H Le David R Goodlett Neil M Nathanson |
| author_facet | Cindy L Reiner Jennifer S McCullar Rebecca L Kow Joshua H Le David R Goodlett Neil M Nathanson |
| author_sort | Cindy L Reiner |
| collection | DOAJ |
| description | Receptor internalization from the cell surface occurs through several mechanisms. Some of these mechanisms, such as clathrin coated pits, are well understood. The M(2) muscarinic acetylcholine receptor undergoes internalization via a poorly-defined clathrin-independent mechanism. We used isotope coded affinity tagging and mass spectrometry to identify the scaffolding protein, receptor for activated C kinase (RACK1) as a protein enriched in M(2)-immunoprecipitates from M(2)-expressing cells over those of non-M(2) expressing cells. Treatment of cells with the agonist carbachol disrupted the interaction of RACK1 with M(2). We further found that RACK1 overexpression inhibits the internalization and subsequent down regulation of the M(2) receptor in a receptor subtype-specific manner. Decreased RACK1 expression increases the rate of agonist internalization of the M(2) receptor, but decreases the extent of subsequent down-regulation. These results suggest that RACK1 may both interfere with agonist-induced sequestration and be required for subsequent targeting of internalized M(2) receptors to the degradative pathway. |
| first_indexed | 2024-04-14T08:17:23Z |
| format | Article |
| id | doaj.art-7856ad320ed747b7b8858e16a60c3b68 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T08:17:23Z |
| publishDate | 2010-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7856ad320ed747b7b8858e16a60c3b682022-12-22T02:04:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-10-01510e1351710.1371/journal.pone.0013517RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking.Cindy L ReinerJennifer S McCullarRebecca L KowJoshua H LeDavid R GoodlettNeil M NathansonReceptor internalization from the cell surface occurs through several mechanisms. Some of these mechanisms, such as clathrin coated pits, are well understood. The M(2) muscarinic acetylcholine receptor undergoes internalization via a poorly-defined clathrin-independent mechanism. We used isotope coded affinity tagging and mass spectrometry to identify the scaffolding protein, receptor for activated C kinase (RACK1) as a protein enriched in M(2)-immunoprecipitates from M(2)-expressing cells over those of non-M(2) expressing cells. Treatment of cells with the agonist carbachol disrupted the interaction of RACK1 with M(2). We further found that RACK1 overexpression inhibits the internalization and subsequent down regulation of the M(2) receptor in a receptor subtype-specific manner. Decreased RACK1 expression increases the rate of agonist internalization of the M(2) receptor, but decreases the extent of subsequent down-regulation. These results suggest that RACK1 may both interfere with agonist-induced sequestration and be required for subsequent targeting of internalized M(2) receptors to the degradative pathway.http://europepmc.org/articles/PMC2958127?pdf=render |
| spellingShingle | Cindy L Reiner Jennifer S McCullar Rebecca L Kow Joshua H Le David R Goodlett Neil M Nathanson RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking. PLoS ONE |
| title | RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking. |
| title_full | RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking. |
| title_fullStr | RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking. |
| title_full_unstemmed | RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking. |
| title_short | RACK1 associates with muscarinic receptors and regulates M(2) receptor trafficking. |
| title_sort | rack1 associates with muscarinic receptors and regulates m 2 receptor trafficking |
| url | http://europepmc.org/articles/PMC2958127?pdf=render |
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