2026-04-13T02:02:48Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1846592025-12-05T10:06:01Zcom_2072_1057col_2072_478916col_2072_478917col_2072_478929

00925njm 22002777a 4500 dc Ferré, Sergi author Ciruela Alférez, Francisco author Dessauer, Carmen W. author González Maeso, Javier author Hébert, Terence E. author Jockers, Ralf author Logothetis, Diomedes E. author Pardo, Leonardo author 2022-04-05T08:19:07Z 2022-04-05T08:19:07Z 2021-02-01 2022-04-05T08:19:08Z 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. Proteïnes G Receptors cel·lulars Membranes cel·lulars G Proteins Cell receptors Cell membranes G protein-coupled receptor-effector macromolecular membrane assemblies (GEMMAs)