Título:
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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
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Autor/a:
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Borroto Escuela, Dasiel O.; Romero Fernández, Wilber; García Negredo, Gloria; Correia, Patricia A.; Garriga, Pere; Fuxe, Kjell; Ciruela Alférez, Francisco
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Otros autores:
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Universitat de Barcelona |
Abstract:
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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. |
Materia(s):
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-Proteïnes G -Receptors colinèrgics -G Proteins -Acetylcholine receptors |
Derechos:
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cc-by-nc (c) Karger, 2011
http://creativecommons.org/licenses/by-nc/3.0/es |
Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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Karger
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Compartir:
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