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Dissecting the conserved NPxxY motif of the M3 muscarinic acetylcholine receptor: critical role of Asp-7.49 for receptor signaling and multiprotein complex formation.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Borroto-Escuela, Dasiel O. Romero-Fernandez, Wilber García-Negredo, Gloria Correia, Patrícia A. Garriga, Pere Fuxe, Kjell Ciruela, Francisco |
| Copyright Year | 2011 |
| Abstract | Acetylcholine challenge produces M(3) muscarinic acetylcholine receptor activation and accessory/scaffold proteins recruitment into a signalsome complex. The dynamics of such a complex is not well understood but a conserved NPxxY motif located within transmembrane 7 and juxtamembrane helix 8 of the receptor was found to modulate G protein activation. Here by means of receptor mutagenesis we unravel the role of the conserved M(3) muscarinic acetylcholine receptor NPxxY motif on ligand binding, signaling and multiprotein complex formation. Interestingly, while a N7.49D receptor mutant showed normal ligand binding properties a N7.49A mutant had reduced antagonist binding and increased affinity for carbachol. Also, besides this last mutant was able to physically couple to Gα(q/11) after carbachol challenge it was neither capable to activate phospholipase C nor phospholipase D. On the other hand, we demonstrated that the Asn-7.49 is important for the interaction between M(3)R and ARF1 and also for the formation of the ARF/Rho/β γ signaling complex, a complex that might determine the rapid activation and desensitization of PLD. Overall, these results indicate that the NPxxY motif of the M(3) muscarinic acetylcholine receptor acts as key conformational switch for receptor signaling and multiprotein complex formation. |
| Starting Page | 876 |
| Ending Page | 883 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.karger.com/Article/Pdf/335788 |
| Alternate Webpage(s) | https://upcommons.upc.edu/bitstream/handle/2117/26206/Dissecting%20the%20Conserved%20NPxxY.pdf;jsessionid=0B83D95FD295BA4BF088F0C7167D348B?sequence=1 |
| PubMed reference number | 22178951v1 |
| Alternate Webpage(s) | https://doi.org/10.1159/000335788 |
| DOI | 10.1159/000335788 |
| Journal | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology |
| Volume Number | 28 |
| Issue Number | 5 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Activation action Affinity Carbachol Cholinergic Receptors Ligand Binding Ligands Muscarinic Acetylcholine Receptor Phospholipase Protein Domain Receptor Activation Process Receptor Signaling hypersensitivity desensitization |
| Content Type | Text |
| Resource Type | Article |
