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 cellul ar signaling systems; this process determines the catalytic lifetime o f the activated receptor and is necessary for response termination. Al though previous work has indicated a class of models in which several sequential steps are required for receptor inactivation, the rate-limi ting event is still unclear. In this paper, we develop a theory that d escribes the kinetics of inactivation of the G protein-coupled recepto r 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 ina ctivation kinetics of activated rhodopsin in vivo and can be independe ntly tested with molecular and spectroscopic data. The results demonst rate that the rate of arrestin binding determines the kinetics of rece ptor inactivation in vivo and thus is the event that controls signal a mplification at the first step of this G protein-coupled transduction cascade.