Membrane protein diffusion sets the speed of rod phototransduction

Retinal rods signal the activation of a single receptor molecule by a photo n(1). To ensure efficient photon capture, rods maintain about 10(9) copies of rhodopsin densely packed into membranous disks(2). But a high packing de nsity of rhodopsin may impede other steps in phototransduction that take pl ace on the disk membrane(3), by restricting the lateral movement of, and he nce the rate of encounters between, the molecules involved(4-6). Although i t has been suggested that lateral diffusion of proteins on the membrane set s the rate of onset of the photoresponse(7), it was later argued that the s ubsequent processing of the complexes was the main determinant of this rate (8,9). The effects of protein density on response shut-off have not been re ported. Here we show that a roughly 50% reduction in protein crowding achie ved by the hemizygous knockout of rhodopsin in transgenic mice accelerates the rising phases and recoveries of flash responses by about 1.7-fold in vi vo. Thus, in rods the rates of both response onset and recovery are set by the diffusional encounter frequency between proteins on the disk membrane.