« Previous AbstractThe effectivenes of Trichotim in control of Cydia pomonella L. in western Romania    Next Abstract"Activation of an essential calcium signaling pathway in Saccharomyces cerevisiae by Kch1 and Kch2, putative low-affinity potassium transporters" »

Mol Biol Cell

Title:		Mechanisms governing the activation and trafficking of yeast G protein-coupled receptors
Author(s):		Stefan CJ; Overton MC; Blumer KJ;
Address:		"Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA"
Journal Title:		Mol Biol Cell
Year:		1998
Volume:		9
Issue:		4
Page Number:		885 - 899
DOI:		10.1091/mbc.9.4.885
ISSN/ISBN:		1059-1524 (Print) 1059-1524 (Linking)
Abstract:		"We have addressed the mechanisms governing the activation and trafficking of G protein-coupled receptors (GPCRs) by analyzing constitutively active mating pheromone receptors (Ste2p and Ste3p) of the yeast Saccharomyces cerevisiae. Substitution of the highly conserved proline residue in transmembrane segment VI of these receptors causes constitutive signaling. This proline residue may facilitate folding of GPCRs into native, inactive conformations, and/or mediate agonist-induced structural changes leading to G protein activation. Constitutive signaling by mutant receptors is suppressed upon coexpression with wild-type, but not G protein coupling-defective, receptors. Wild-type receptors may therefore sequester a limiting pool of G proteins; this apparent 'precoupling' of receptors and G proteins could facilitate signal production at sites where cell surface projections form during mating partner discrimination. Finally, rather than being expressed mainly at the cell surface, constitutively active pheromone receptors accumulate in post-endoplasmic reticulum compartments. This is in contrast to other defective membrane proteins, which apparently are targeted by default to the vacuole. We suggest that the quality-control mechanism that retains receptors in post-endoplasmic reticulum compartments may normally allow wild-type receptors to fold into their native, fully inactive conformations before reaching the cell surface. This may ensure that receptors do not trigger a response in the absence of agonist"
Keywords:		"Amino Acid Sequence Binding Sites Conserved Sequence Fungal Proteins/*metabolism GTP-Binding Proteins/*metabolism Gene Expression Regulation, Fungal Molecular Sequence Data Mutation Pheromones/pharmacology Proline Receptors, Cell Surface/*genetics/metabol;"
Notes:		"MedlineStefan, C J Overton, M C Blumer, K J eng GM-44592/GM/NIGMS NIH HHS/ Research Support, U.S. Gov't, P.H.S. 1998/05/16 Mol Biol Cell. 1998 Apr; 9(4):885-99. doi: 10.1091/mbc.9.4.885"