Arrestin binding determines the rate of inactivation of the G protein-coupled receptor rhodopsin in vivo.
G protein-coupled receptor inactivation is a crucial feature of cellular signaling systems; this process determines the catalytic lifetime of the activated receptor and is necessary for response termination. Although previous work has indicated a class of models in which several sequential steps are required for receptor inactivation, the rate-limiting event is still unclear. In this paper, we develop a theory that describes the kinetics of inactivation of the G protein-coupled receptor rhodopsin based on the rate of arrestin binding and test the theory using a combination of genetic and electrophysiological techniques in Drosophila photoreceptors. The theory quantitatively describes the inactivation kinetics of activated rhodopsin in vivo and can be independently tested with molecular and spectroscopic data. The results demonstrate that the rate of arrestin binding determines the kinetics of receptor inactivation in vivo and thus is the event that controls signal amplification at the first step of this G protein-coupled transduction cascade.
Ranganathan
R
R
Howard Hughes Medical Institute, Department of Biology, University of California, San Diego, USA.
Stevens
C F
CF
D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D019393:Arrestin; D004330:Drosophila; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008954:Models, Biological; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012243:Rhodopsin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000941:Antigens; D019393:Arrestin; D005136:Eye Proteins; D011956:Receptors, Cell Surface; C013110:metarhodopsins; D012243:Rhodopsin; D019204:GTP-Binding Proteins