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http://hdl.handle.net/2445/126278
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DC Field | Value | Language |
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dc.contributor.author | Borroto Escuela, Dasiel Oscar | - |
dc.contributor.author | Romero Fernández, Wilber | - |
dc.contributor.author | García Negredo, Gloria | - |
dc.contributor.author | Correia, Patricia A. | - |
dc.contributor.author | Garriga, Pere | - |
dc.contributor.author | Fuxe, Kjell | - |
dc.contributor.author | Ciruela Alférez, Francisco | - |
dc.date.accessioned | 2018-11-21T11:10:30Z | - |
dc.date.available | 2018-11-21T11:10:30Z | - |
dc.date.issued | 2011-12-15 | - |
dc.identifier.issn | 1015-8987 | - |
dc.identifier.uri | http://hdl.handle.net/2445/126278 | - |
dc.description.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 G alpha(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 M3R and ARF1 and also for the formation of the ARF/Rho/beta gamma 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. | - |
dc.format.extent | 14 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Karger | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1159/000335788 | - |
dc.relation.ispartof | Cellular Physiology and Biochemistry, 2011, vol. 28, num. 5, p. 1009-1022 | - |
dc.relation.uri | https://doi.org/10.1159/000335788 | - |
dc.rights | cc-by-nc (c) Karger, 2011 | - |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/es | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Proteïnes G | - |
dc.subject.classification | Receptors colinèrgics | - |
dc.subject.other | G Proteins | - |
dc.subject.other | Acetylcholine receptors | - |
dc.title | Dissecting the conserved NPxxY motif of the M<sub>3</sub> muscarinic acetylcholine receptor: critical role of Asp-7.49 for receptor signaling and multiprotein complex formation | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 601085 | - |
dc.date.updated | 2018-11-21T11:10:30Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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601085.pdf | 915.12 kB | Adobe PDF | View/Open |
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