New roles for Galpha and RGS proteins: communication continues despite pulling sisters apart.
Large G protein alpha subunits and their attendant regulators of G-protein signaling (RGS) proteins control both intercellular signaling and asymmetric cell divisions by distinct pathways. The classical pathway, found throughout higher eukaryotic organisms, mediates intercellular communication via hormone binding to G-protein-coupled receptors (GPCRs). Recent studies have led to the discovery of GPCR-independent activation of Galpha subunits by the guanine nucleotide exchange factor RIC-8 in both asymmetric cell division and synaptic vesicle priming in metazoan organisms. Protein-protein interactions and protein function in each pathway are driven through the cycle of GTP binding and hydrolysis by the Galpha subunit. This review builds a conceptual framework for understanding RIC-8-mediated pathways by comparison with the mechanism of classical G-protein activation and inhibition in GPCR signaling.
Wilkie
Thomas M
TM
Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA. thomas.wilke@utsouthwestern.edu
Kinch
Lisa
L
D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics / Q000502:physiology*; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors; D006728:Hormones / Q000378:metabolism; D008870:Microtubules / Q000502:physiology; D008954:Models, Biological; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D044385:GTP-Binding Protein alpha Subunits; D020662:Guanine Nucleotide Exchange Factors; D006728:Hormones; D009687:Nuclear Proteins; D020710:RGS Proteins; C413418:RIC-8 protein, C elegans; D043562:Receptors, G-Protein-Coupled