UCLA

Structural studies on the cGMP-specific phosphodiesterase (PDE6) found in vertebrate rod photoreceptors (PDE6) reveal that in addition to its two catalytic binding sites, PDE6 possesses two noncatalytic sites that also bind cGMP. These sites are thought potentially to influence the mechanism through which vertebrate photoreceptors adapt to light. By assessing the electrophysiological response via suction-electrode recordings of transgenic mice (NCBS-1) which have a knockout of one of the two noncatalytic sites, we determined whether there were changes in the physiological amplitude and time course of the photoresponse. We are able to characterize the presence of an altered phenotype in the NCBS-1 rod light response, wherein the waveform is lengthened and responses for similar intensities of light are larger than those in the wild-type mouse. These results confirm a modest alteration of the adaptation mechanism but show that the non-catalytic sites in some way control expression or trafficking of the PDE6.