Transducin and the cyclic GMP phosphodiesterase: amplifier proteins in vision.
Our experiments have delineated the flow of information in the cyclic nucleotide cascade of vision of ROS. A single, photoexcited rhodopsin molecule activates several hundred phosphodiesterase molecules in two stages. First, photoexcited rhodopsin (R*) interacts with transducin (T), a peripheral membrane protein consisting of alpha- (39 kD), beta- (36 kD), and gamma- (approximately 10 kD) subunits. R* catalyzes the exchange of GTP for GDP bound to the subunit of transducin. About 500 T alpha- GTPs are produced per photoexcited rhodopsin at low light levels. T alpha-GTP, released from the beta- and gamma-subunits of transducin, then interacts with the phosphodiesterase to relieve the inhibitory constraint imposed by its gamma-subunit. Hydrolysis of GTP bound to T alpha serves to restore the system to the dark state. Transducin is the amplified signal carrier in this light-triggered cascade. The formation of hundreds of T alpha- GTPs is likely to be the first stage of amplification in visual excitation. The photoactivation of the phosphodiesterase in ROS closely resembles the activation of adenylate cyclase in hormone-sensitive cells. Our cholera toxin labeling studies have shown that transducin is akin to the signal-coupling G protein of the adenylate cyclase system. Cholera toxin specifically ADP- ribosylates and inactivates the GTPase activity of T alpha, just as it does with Gs. The action of pertussis toxin on ROS further underscores the homology of the photoreceptor and hormone-responsive systems. It seems likely that transducin, the stimulatory G protein, and the inhibitory G protein are members of the same family of signal-amplifying proteins. The study of the cyclic nucleotide cascade of vision is proving to be rewarding in affording a view of a recurring motif of signal amplification in nature in addition to providing insight into the mechanism of vision.
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D008027:Light; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D010782:Photolysis; D010786:Photoreceptor Cells / Q000502:physiology*; D012168:Retinal Pigments / Q000378:metabolism*; D012243:Rhodopsin / Q000378:metabolism*; D015293:Transducin; D014357:Trypsin / Q000494:pharmacology; D014785:Vision, Ocular
D046911:Macromolecular Substances; D008565:Membrane Proteins; D012168:Retinal Pigments; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D012243:Rhodopsin; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D014357:Trypsin; D015293:Transducin