Interactions between intracellular domains as key determinants of the quaternary structure and function of receptor heteromers

G protein-coupled receptor (GPCR) heteromers are macromolecular complexes with unique functional properties different from those of its individual protomers. Little is known about what determines the quaternary structure of GPCR heteromers resulting in their unique functional properties. In the pres...

Full description

Bibliographic Details
Authors: Navarro Brugal, Gemma, Ferré, Sergi, Cordomí, Arnau, Moreno Guillén, Estefanía, Mallol Montero, Josefa, Casadó, Vicent, Cortés Tejedor, Antonio, Hoffmann, Hanne, Ortiz, Jordi, Canela Campos, Enric I. (Enric Isidre), 1949-, Lluís i Biset, Carme, Pardo, Leonardo, Franco Fernández, Rafael, Woods, Amina S.
Format: article
Status:Published version
Publication Date:2010
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/122533
Online Access:https://hdl.handle.net/2445/122533
Access Level:Open access
Keyword:Receptors cel·lulars
Interacció cel·lular
Cell receptors
Cell interaction
id ES_baea0fad72d2edd027f5fadf1f2dd76c
oai_identifier_str oai:diposit.ub.edu:2445/122533
network_acronym_str ES
network_name_str España
repository_id_str
spelling Interactions between intracellular domains as key determinants of the quaternary structure and function of receptor heteromersNavarro Brugal, GemmaFerré, SergiCordomí, ArnauMoreno Guillén, EstefaníaMallol Montero, JosefaCasadó, VicentCortés Tejedor, AntonioHoffmann, HanneOrtiz, JordiCanela Campos, Enric I. (Enric Isidre), 1949-Lluís i Biset, CarmePardo, LeonardoFranco Fernández, RafaelWoods, Amina S.Receptors cel·lularsInteracció cel·lularCell receptorsCell interactionG protein-coupled receptor (GPCR) heteromers are macromolecular complexes with unique functional properties different from those of its individual protomers. Little is known about what determines the quaternary structure of GPCR heteromers resulting in their unique functional properties. In the present study, using Resonance Energy Transfer (RET) techniques in experiments with mutated receptors, we provide for the first time clear evidence for a key role of intracellular domains in the determination of the quaternary structure of GPCR heteromers between adenosine A2A, cannabinoid CB1 and dopamine D2 receptors. In these interactions, arginine-rich epitopes form salt bridges with phosphorylated serine or threonine residues from CK1/2 consensus sites. Each receptor (A2A, CB1 and D2) was found to include two evolutionary conserved intracellular domains to establish selective electrostatic interactions with intracellular domains of the other two receptors, indicating that these particular electrostatic interactions constitute a general mechanism for receptor heteromerization. Mutation experiments indicated that the interactions of the intracellular domains of the CB1 receptor with A2A and D2 receptors are fundamental for the correct formation of the quaternary structure needed for the function (mitogen-activated protein kinase, MAPK, signaling) of the A2A-CB1-D2 receptor heteromers. Analysis of MAPK signaling in striatal slices of CB1 receptor KO mice and wild-type littermates supported the existence of A1-CB1-D2 receptor heteromer in the brain. These findings allowed us to propose the first molecular model of the quaternary structure of a receptor heteromultimerAmerican Society for Biochemistry and Molecular Biology2010info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/122533Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1074/jbc.M110.115634Journal of Biological Chemistry, 2010, vol. 285, num. 35, p. 27346-27359https://doi.org/10.1074/jbc.M110.115634(c) American Society for Biochemistry and Molecular Biology, 2010info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1225332026-05-27T06:46:51Z
dc.title.none.fl_str_mv Interactions between intracellular domains as key determinants of the quaternary structure and function of receptor heteromers
title Interactions between intracellular domains as key determinants of the quaternary structure and function of receptor heteromers
spellingShingle Interactions between intracellular domains as key determinants of the quaternary structure and function of receptor heteromers
Navarro Brugal, Gemma
Receptors cel·lulars
Interacció cel·lular
Cell receptors
Cell interaction
title_short Interactions between intracellular domains as key determinants of the quaternary structure and function of receptor heteromers
title_full Interactions between intracellular domains as key determinants of the quaternary structure and function of receptor heteromers
title_fullStr Interactions between intracellular domains as key determinants of the quaternary structure and function of receptor heteromers
title_full_unstemmed Interactions between intracellular domains as key determinants of the quaternary structure and function of receptor heteromers
title_sort Interactions between intracellular domains as key determinants of the quaternary structure and function of receptor heteromers
dc.creator.none.fl_str_mv Navarro Brugal, Gemma
Ferré, Sergi
Cordomí, Arnau
Moreno Guillén, Estefanía
Mallol Montero, Josefa
Casadó, Vicent
Cortés Tejedor, Antonio
Hoffmann, Hanne
Ortiz, Jordi
Canela Campos, Enric I. (Enric Isidre), 1949-
Lluís i Biset, Carme
Pardo, Leonardo
Franco Fernández, Rafael
Woods, Amina S.
author Navarro Brugal, Gemma
author_facet Navarro Brugal, Gemma
Ferré, Sergi
Cordomí, Arnau
Moreno Guillén, Estefanía
Mallol Montero, Josefa
Casadó, Vicent
Cortés Tejedor, Antonio
Hoffmann, Hanne
Ortiz, Jordi
Canela Campos, Enric I. (Enric Isidre), 1949-
Lluís i Biset, Carme
Pardo, Leonardo
Franco Fernández, Rafael
Woods, Amina S.
author_role author
author2 Ferré, Sergi
Cordomí, Arnau
Moreno Guillén, Estefanía
Mallol Montero, Josefa
Casadó, Vicent
Cortés Tejedor, Antonio
Hoffmann, Hanne
Ortiz, Jordi
Canela Campos, Enric I. (Enric Isidre), 1949-
Lluís i Biset, Carme
Pardo, Leonardo
Franco Fernández, Rafael
Woods, Amina S.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Receptors cel·lulars
Interacció cel·lular
Cell receptors
Cell interaction
topic Receptors cel·lulars
Interacció cel·lular
Cell receptors
Cell interaction
description G protein-coupled receptor (GPCR) heteromers are macromolecular complexes with unique functional properties different from those of its individual protomers. Little is known about what determines the quaternary structure of GPCR heteromers resulting in their unique functional properties. In the present study, using Resonance Energy Transfer (RET) techniques in experiments with mutated receptors, we provide for the first time clear evidence for a key role of intracellular domains in the determination of the quaternary structure of GPCR heteromers between adenosine A2A, cannabinoid CB1 and dopamine D2 receptors. In these interactions, arginine-rich epitopes form salt bridges with phosphorylated serine or threonine residues from CK1/2 consensus sites. Each receptor (A2A, CB1 and D2) was found to include two evolutionary conserved intracellular domains to establish selective electrostatic interactions with intracellular domains of the other two receptors, indicating that these particular electrostatic interactions constitute a general mechanism for receptor heteromerization. Mutation experiments indicated that the interactions of the intracellular domains of the CB1 receptor with A2A and D2 receptors are fundamental for the correct formation of the quaternary structure needed for the function (mitogen-activated protein kinase, MAPK, signaling) of the A2A-CB1-D2 receptor heteromers. Analysis of MAPK signaling in striatal slices of CB1 receptor KO mice and wild-type littermates supported the existence of A1-CB1-D2 receptor heteromer in the brain. These findings allowed us to propose the first molecular model of the quaternary structure of a receptor heteromultimer
publishDate 2010
dc.date.none.fl_str_mv 2010
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/122533
url https://hdl.handle.net/2445/122533
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1074/jbc.M110.115634
Journal of Biological Chemistry, 2010, vol. 285, num. 35, p. 27346-27359
https://doi.org/10.1074/jbc.M110.115634
dc.rights.none.fl_str_mv (c) American Society for Biochemistry and Molecular Biology, 2010
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Biochemistry and Molecular Biology, 2010
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869417979150598144
score 15,300719

Similar Items