GAIN AND KINETICS OF ACTIVATION IN THE G-PROTEIN CASCADE OF PHOTOTRANSDUCTION

The guanine nucleotide binding protein (G protein) cascade underlying phototransduction is one of the best understood of all signaling pathw ays. The diffusional interactions of the proteins underlying the casca de have been analyzed, both at a macroscopic level and also in terms o f the stochastic nature of the molecular contacts. In response to a si ngle activated rhodopsin (R) formed as a result of a single photon hi t, it can be shown that molecules of the G-protein transducin will be activated approximately linearly with time. This, in turn, will cause the number of activated molecules of the effector protein (the phospho diesterase) also to increase linearly with time. These kinetics of pro tein activation provide an accurate description of the time course of the rising phase of the photoreceptor's electrical response over a wid e range of flash intensities, Recent estimates indicate that at room t emperature each R triggers activation of the phosphodiesterase at a r ate of 1000-2000 subunits . s(-1). Now that a quantitative description of the activation steps in transduction has been obtained, perhaps th e greatest challenge for the future is to provide a comprehensive desc ription of the shutoff reactions, so that a complete account of the ph otoreceptor's response to light can be achieved.