Persistent membrane association of activated and depalmitoylated G protein alpha subunits.
Heterotrimeric signal-transducing G proteins are organized at the inner surface of the plasma membrane, where they are positioned to interact with membrane-spanning receptors and appropriate effectors. G proteins are activated when they bind GTP and inactivated when they hydrolyze the nucleotide to GDP. However, the topological fate of activated G protein alpha subunits is disputed. One model declares that depalmitoylation of alpha, which accompanies activation by a receptor, promotes release of the protein into the cytoplasm. Our data suggest that activation of G protein alpha subunits causes them to concentrate in subdomains of the plasma membrane but not to be released from the membrane. Furthermore, alpha subunits remained bound to the membrane when they were activated with guanosine 5'-(3-O-thio)triphosphate and depalmitoylated with an acyl protein thioesterase. Limitation of alpha subunits to the plasma membrane obviously restricts their mobility and may contribute to the efficiency and specificity of signaling.
Huang
C
C
University of Texas Southwestern Medical Center, Department of Pharmacology, 5323 Harry Hines Boulevard, Dallas, TX 75235-9041, USA.
Duncan
J A
JA
Gilman
A G
AG
Mumby
S M
SM
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008253:Macaca mulatta; D008565:Membrane Proteins / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism*; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection / Q000235:genetics
D008565:Membrane Proteins; D019308:Palmitic Acid; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010170:Palmitoyl-CoA Hydrolase; D019204:GTP-Binding Proteins