Gαq signalling: the new and the old.
In the last few years the interactome of Gαq has expanded considerably, contributing to improve our understanding of the cellular and physiological events controlled by this G alpha subunit. The availability of high-resolution crystal structures has led the identification of an effector-binding region within the surface of Gαq that is able to recognise a variety of effector proteins. Consequently, it has been possible to ascribe different Gαq functions to specific cellular players and to identify important processes that are triggered independently of the canonical activation of phospholipase Cβ (PLCβ), the first identified Gαq effector. Novel effectors include p63RhoGEF, that provides a link between G protein-coupled receptors and RhoA activation, phosphatidylinositol 3-kinase (PI3K), implicated in the regulation of the Akt pathway, or the cold-activated TRPM8 channel, which is directly inhibited upon Gαq binding. Recently, the activation of ERK5 MAPK by Gq-coupled receptors has also been described as a novel PLCβ-independent signalling axis that relies upon the interaction between this G protein and two novel effectors (PKCζ and MEK5). Additionally, the association of Gαq with different regulatory proteins can modulate its effector coupling ability and, therefore, its signalling potential. Regulators include accessory proteins that facilitate effector activation or, alternatively, inhibitory proteins that downregulate effector binding or promote signal termination. Moreover, Gαq is known to interact with several components of the cytoskeleton as well as with important organisers of membrane microdomains, which suggests that efficient signalling complexes might be confined to specific subcellular environments. Overall, the complex interaction network of Gαq underlies an ever-expanding functional diversity that puts forward this G alpha subunit as a major player in the control of physiological functions and in the development of different pathological situations.
Departamento de Biología Molecular and Centro de Biologia Molecular "Severo Ochoa", CSIC-UAM, Universidad Autónoma de Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, Madrid, Spain.
Guzmán
G
Sánchez-Fernández
Departamento de Biología Molecular and Centro de Biologia Molecular "Severo Ochoa", CSIC-UAM, Universidad Autónoma de Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, Madrid, Spain.
Sofía
S
Cabezudo
Departamento de Biología Molecular and Centro de Biologia Molecular "Severo Ochoa", CSIC-UAM, Universidad Autónoma de Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, Madrid, Spain.
Carlota
C
García-Hoz
Department of Cardiovascular Development and Repair, CNIC, Spain.
Cristiane
C
Benincá
Department of Cell Biology, Molecular Biology Institute of Barcelona, Spain.
Anna M
AM
Aragay
Departamento de Biología Molecular and Centro de Biologia Molecular "Severo Ochoa", CSIC-UAM, Universidad Autónoma de Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, Madrid, Spain.
Federico
F
Mayor
Departamento de Biología Molecular and Centro de Biologia Molecular "Severo Ochoa", CSIC-UAM, Universidad Autónoma de Madrid, Spain; Instituto de Investigación Sanitaria La Princesa, Madrid, Spain. Electronic address: cribas@cbm.uam.es.
Catalina
C
Ribas
D060833:Cellular Microenvironment; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D048671:MAP Kinase Kinase 5 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D054799:Phospholipase C beta / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D043562:Receptors, G-Protein-Coupled; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048671:MAP Kinase Kinase 5; D054799:Phospholipase C beta; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020742:rhoA GTP-Binding Protein
G protein; G-protein coupled receptors; Gq; Interactome; Signalling pathways