RT Journal Article
T1 Impaired M 3 Muscarinic acetylcholine receptor signal transduction through blockade of binding of multiple proteins to its third intracellular loop
A1 Borroto Escuela, Dasiel Óscar
A1 Correia, Patricia A.
A1 Pérez Alea, Mileidys
A1 Narváez-Peláez, Manuel
A1 Garriga, Pere
A1 Fuxe, Kjell
A1 Ciruela, Francisco
K1 Receptores colinérgicos
K1 Proteínas G
K1 Neurorreceptores
AB Several motifs found in the third intracellular loop of the M 3 muscarinic receptor are critical for G protein activation and scaffold protein interaction. However, how multiprotein complexes form is not fully understood. A minigene encoding the third intracellular loop of the M 3 muscarinic receptor was constructed to explore whether peptides from this intracellular region could act as inhibitors of the muscarinic multiprotein complex formation and signaling. We found that this construct, when co-expressed with the M 3 receptor, has the ability to act as a competitive antagonist of G protein receptors and receptor-scaffold/accessory proteins. Transient transfection of human embryonic kidney-293 cells with DNA encoding the human M 3 and M 5 receptor subtypes results in a carbachol-dependent increase of inositol phosphate. Co-expression of the M 3 third cytoplasmic loop minigene dramatically reduces both carbachol-mediated G protein activation and inositol phosphate accumulation. Minigene expression also abrogates activation of M 3 and M 5 receptor mitogen-activated protein kinases pathway. Furthermore, minigene expression led to reduced AKT activation. These data, together with results of co-immunoprecipitation of different scaffold and kinase proteins, provide experimental evidence for the role for the third cytoplasmic loop of the human M 3 muscarinic receptor in G-protein activation and multiprotein complex formation.
PB Karger
SN 1015-8987
YR 2010
FD 2010-03-23
LK https://hdl.handle.net/10630/44999
UL https://hdl.handle.net/10630/44999
LA eng
NO Dasiel O. Borroto-Escuela, Patricia A. Correia, Mileidys Perez Alea, Manuel Narvaez, Pere Garriga, Kjell Fuxe, Francisco Ciruela; Impaired M3 Muscarinic Acetylcholine Receptor Signal Transduction Through Blockade of Binding of Multiple Proteins to its Third Intracellular Loop. Cellular Physiology and Biochemistry 1 March 2010; 25 (4-5): 397–408. https://doi-org.proxy.kib.ki.se/10.1159/000303044
NO https://karger.com/pages/rights-and-permissions
NO Ministerio de Ciencia e Innovación (Gobierno de España)
NO European Social Fund (FSE/ESF)
NO Generalitat de Catalunya (Govern de Catalunya)
NO Swedish Medical Research Council
NO Torsten and Ragnar Söderberg Foundation
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 28 feb 2026