Millisecond activation of transducin in the cyclic nucleotide cascade of vision

Cyclic GMP has been implicated as a messenger molecule involved in visual transduction. Photoexcited rhodopsin (R*) binds to a multisubunit membrane protein called transducin (T) and stimulates the exchange of a bound GDP molecule for GTP. This leads to the release of the alpha-subunit of T with bound GTP (T alpha-GTP), which activates a cyclic GMP phosphodiesterase. The question arises as to whether the hydrolysis of cyclic GMP that results from activation of the phosphodiesterase is sufficiently rapid to be involved in visual excitation, which occurs on a time scale of approximately 2 s in the single-photon limit. Previous studies have suggested that the cyclic GMP phosphodiesterase is activated in less than 100 ms at moderate light levels. We report here light scattering studies of magnetically orientated frog rod outer segments which show that a molecule of R* catalyses the activation of a molecule of T in about 1 ms. Thus, hundreds of molecules can be activated within the response time of vision in the single-photon limit, and the formation of T alpha-GTP is fast enough for it to be a key step in visual transduction.