Amb motiu del tancament d'estiu, la validació de documents es reprendrà a partir del 28 d'agost de 2026. Disculpeu les molèsties.
Con motivo del cierre de verano, la validación de documentos se reanudará a partir del 28 de agosto de 2026. Disculpad las molestias
Due to the summer closure, document validation will resume starting August 28, 2026. We apologize for any inconvenience.

Files

601085.pdf (915.12 KB)

Document type

Article

Version

Published version

Publication date

2011-12-15

Publication license

cc-by-nc (c) Karger, 2011
Please use this identifier to cite or link to this item: 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

Journal Title

Authors

Director/Tutor

Journal ISSN

Volume Title

Related resource

https://doi.org/10.1159/000335788

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.

Subject

Proteïnes G, Receptors colinèrgics

Subject (English)

G Proteins, Acetylcholine receptors

Citation

Collections

Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citation

BORROTO ESCUELA, Dasiel Oscar, et al. Dissecting the conserved NPxxY motif of the M3 muscarinic acetylcholine receptor: critical role of Asp-7.49 for receptor signaling and multiprotein complex formation. Cellular Physiology and Biochemistry. 2011. Vol. 28, num. 5, pags. 1009-1022. ISSN 1015-8987. [consulted: 10 of August of 2026]. Available at: https://hdl.handle.net/2445/126278

Export metadata

JSON - METS

Share record