Persistent Membrane Association of Activated and Depalmitoylated G Protein α subunits

• Published in: Proceedings of the National Academy of Sciences - PNAS 1999-01, Vol.96 (2), p.412-417
• Main Authors: Huang, Chunfa, Duncan, Joseph A., Gilman, Alfred G., Mumby, Susanne M.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Biochemistry; Biological Sciences; Cell Line; Cell Membrane - metabolism; Cell membranes; Cellular immunity; COS cells; Fluorescent antibody techniques; GTP-Binding Proteins - metabolism; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Humans; Immunohistochemistry; Macaca mulatta; Membrane Proteins - metabolism; Membranes; Nucleotides; P branes; Palmitates; Palmitic Acid - metabolism; Palmitoyl-CoA Hydrolase - metabolism; Plasma interactions; Proteins; Receptors; Signal Transduction; Transfection - genetics
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.2.412

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 α subunits is disputed. One model declares that depalmitoylation of α, which accompanies activation by a receptor, promotes release of the protein into the cytoplasm. Our data suggest that activation of G protein α subunits causes them to concentrate in subdomains of the plasma membrane but not to be released from the membrane. Furthermore, α 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 α subunits to the plasma membrane obviously restricts their mobility and may contribute to the efficiency and specificity of signaling.