G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs)

G protein-coupled receptors (GPCRs) are the largest group of receptors involved in cellular signaling across the plasma membrane and a major class of drug targets. The canonical model for GPCR signaling involves three components the GPCR, a heterotrimeric G protein and a proximal plasma membrane eff...

Full description

Bibliographic Details
Authors: Ferré, Sergi, Ciruela Alférez, Francisco, Dessauer, Carmen W., González Maeso, Javier, Hébert, Terence E., Jockers, Ralf, Logothetis, Diomedes E., Pardo, Leonardo
Format: article
Status:Published version
Publication Date:2021
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/184659
Online Access:https://hdl.handle.net/2445/184659
Access Level:Open access
Keyword:Proteïnes G
Receptors cel·lulars
Membranes cel·lulars
G Proteins
Cell receptors
Cell membranes
id ES_b62c510ca3e7bcfb06f07deed05efaf7
oai_identifier_str oai:diposit.ub.edu:2445/184659
network_acronym_str ES
network_name_str España
repository_id_str
spelling G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs)Ferré, SergiCiruela Alférez, FranciscoDessauer, Carmen W.González Maeso, JavierHébert, Terence E.Jockers, RalfLogothetis, Diomedes E.Pardo, LeonardoProteïnes GReceptors cel·lularsMembranes cel·lularsG ProteinsCell receptorsCell membranesG protein-coupled receptors (GPCRs) are the largest group of receptors involved in cellular signaling across the plasma membrane and a major class of drug targets. The canonical model for GPCR signaling involves three components the GPCR, a heterotrimeric G protein and a proximal plasma membrane effector that have been generally thought to be freely mobile molecules able to interact by 'collision coupling'. Here, we synthesize evidence that supports the existence of GPCR-effector macromolecular membrane assemblies (GEMMAs) comprised of specific GPCRs, G proteins, plasma membrane effector molecules and other associated transmembrane proteins that are pre-assembled prior to receptor activation by agonists, which then leads to subsequent rearrangement of the GEMMA components. The GEMMA concept offers an alternative and complementary model to the canonical collision-coupling model, allowing more efficient interactions between specific signaling components, as well as the integration of the concept of GPCR oligomerization as well as GPCR interactions with orphan receptors, truncated GPCRs and other membrane-localized GPCR-associated proteins. Collision-coupling and pre-assembled mechanisms are not exclusive and likely both operate in the cell, providing a spectrum of signaling modalities which explains the differential properties of a multitude of GPCRs in their different cellular environments. Here, we explore the unique pharmacological characteristics of individual GEMMAs, which could provide new opportunities to therapeutically modulate GPCR signaling.Elsevier2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/184659Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1016/j.pharmthera.2021.107977Pharmacology & Therapeutics, 2021, vol. 231, p. 107977https://doi.org/10.1016/j.pharmthera.2021.107977cc-by-nc-nd (c) Ferré, Sergi et al., 2021https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1846592026-05-27T06:46:51Z
dc.title.none.fl_str_mv G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs)
title G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs)
spellingShingle G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs)
Ferré, Sergi
Proteïnes G
Receptors cel·lulars
Membranes cel·lulars
G Proteins
Cell receptors
Cell membranes
title_short G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs)
title_full G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs)
title_fullStr G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs)
title_full_unstemmed G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs)
title_sort G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs)
dc.creator.none.fl_str_mv Ferré, Sergi
Ciruela Alférez, Francisco
Dessauer, Carmen W.
González Maeso, Javier
Hébert, Terence E.
Jockers, Ralf
Logothetis, Diomedes E.
Pardo, Leonardo
author Ferré, Sergi
author_facet Ferré, Sergi
Ciruela Alférez, Francisco
Dessauer, Carmen W.
González Maeso, Javier
Hébert, Terence E.
Jockers, Ralf
Logothetis, Diomedes E.
Pardo, Leonardo
author_role author
author2 Ciruela Alférez, Francisco
Dessauer, Carmen W.
González Maeso, Javier
Hébert, Terence E.
Jockers, Ralf
Logothetis, Diomedes E.
Pardo, Leonardo
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Proteïnes G
Receptors cel·lulars
Membranes cel·lulars
G Proteins
Cell receptors
Cell membranes
topic Proteïnes G
Receptors cel·lulars
Membranes cel·lulars
G Proteins
Cell receptors
Cell membranes
description G protein-coupled receptors (GPCRs) are the largest group of receptors involved in cellular signaling across the plasma membrane and a major class of drug targets. The canonical model for GPCR signaling involves three components the GPCR, a heterotrimeric G protein and a proximal plasma membrane effector that have been generally thought to be freely mobile molecules able to interact by 'collision coupling'. Here, we synthesize evidence that supports the existence of GPCR-effector macromolecular membrane assemblies (GEMMAs) comprised of specific GPCRs, G proteins, plasma membrane effector molecules and other associated transmembrane proteins that are pre-assembled prior to receptor activation by agonists, which then leads to subsequent rearrangement of the GEMMA components. The GEMMA concept offers an alternative and complementary model to the canonical collision-coupling model, allowing more efficient interactions between specific signaling components, as well as the integration of the concept of GPCR oligomerization as well as GPCR interactions with orphan receptors, truncated GPCRs and other membrane-localized GPCR-associated proteins. Collision-coupling and pre-assembled mechanisms are not exclusive and likely both operate in the cell, providing a spectrum of signaling modalities which explains the differential properties of a multitude of GPCRs in their different cellular environments. Here, we explore the unique pharmacological characteristics of individual GEMMAs, which could provide new opportunities to therapeutically modulate GPCR signaling.
publishDate 2021
dc.date.none.fl_str_mv 2021
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/2445/184659
url https://hdl.handle.net/2445/184659
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/10.1016/j.pharmthera.2021.107977
Pharmacology & Therapeutics, 2021, vol. 231, p. 107977
https://doi.org/10.1016/j.pharmthera.2021.107977
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Ferré, Sergi et al., 2021
https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Ferré, Sergi et al., 2021
https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
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_ 1869417424610131968
score 15,300719

Similar Items