Cell adhesion receptor GPR133 couples to Gs protein.
Adhesion G protein-coupled receptors (GPCR), with their very large and complex N termini, are thought to participate in cell-cell and cell-matrix interactions and appear to be highly relevant in several developmental processes. Their intracellular signaling is still poorly understood. Here we demonstrate that GPR133, a member of the adhesion GPCR subfamily, activates the G(s) protein/adenylyl cyclase pathway. The presence of the N terminus and the cleavage at the GPCR proteolysis site are not required for G protein signaling. G(s) protein coupling was verified by Gα(s) knockdown with siRNA, overexpression of Gα(s), co-expression of the chimeric Gq(s4) protein that routes GPR133 activity to the phospholipase C/inositol phosphate pathway, and missense mutation within the transmembrane domain that abolished receptor activity without changing cell surface expression. It is likely that not only GPR133 but also other adhesion GPCR signal via classical receptor/G protein-interaction.
Section of Molecular Biochemistry, Institute of Biochemistry, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany.
Jens
J
Bohnekamp
Section of Molecular Biochemistry, Institute of Biochemistry, Medical Faculty, University of Leipzig, 04103 Leipzig, Germany. Electronic address: schoberg@medizin.uni-leipzig.de.
Torsten
T
Schöneberg
D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002450:Cell Communication; D002460:Cell Line; D002522:Chlorocebus aethiops; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D006801:Humans; D051379:Mice; D020125:Mutation, Missense; D034741:RNA, Small Interfering / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
C547021:ADGRD1 protein, human; D015815:Cell Adhesion Molecules; C570108:GPR133 protein, mouse; D044385:GTP-Binding Protein alpha Subunits; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled