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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/126278
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
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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.
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BORROTO ESCUELA, Dasiel oscar, ROMERO FERNÁNDEZ, Wilber, GARCÍA NEGREDO, Gloria, CORREIA, Patricia a., GARRIGA, Pere, FUXE, Kjell, CIRUELA ALFÉREZ, Francisco. 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. _Cellular Physiology and Biochemistry_. 2011. Vol. 28, núm. 5, pàgs. 1009-1022. [consulta: 24 de gener de 2026]. ISSN: 1015-8987. [Disponible a: https://hdl.handle.net/2445/126278]