The rod photoreceptor and the disc-associated proteins that mediate the response to lightĪ: rod photoreceptors are highly compartmentalized cells, with most organelles retained in the inner segment (IS) and synaptic ending (SE). For a more detailed, historically developed perspective on the activation reactions, see other reviews (e.g., Refs. The resulting fall in the cGMP concentration causes the cGMP-gated channels in the plasma membrane to close ( 21, 51), leading to membrane hyperpolarization that reduces the rate of glutamate release onto second-order retinal neurons. Each activated transducin alpha subunit (G tα-GTP hereafter G*), binds to the gamma subunit of the cGMP phosphodiesterase (PDEγ), relieving its inhibition of the PDE6 catalytic subunits ( 50, 122) the activated transducin-PDE6 complex (G*-E*) hydrolyzes cGMP. R* catalyzes GDP/GTP exchange on multiple copies of the heterotrimeric G-protein transducin. The biochemical events that initiate signaling are known in detail ( FIGURE 1B): the absorption of a photon isomerizes the 11- cis retinal chromophore of rhodopsin ( 120), triggering a conformational change to a catalytically active state within milliseconds. In rods, the molecular machinery of the cascade is concentrated in the outer segment, a subcellular reaction chamber containing several thousand square microns of highly structured, protein-laden membranes, the disc stack ( FIGURE 1A).
Reduced gain faster recovery in RGS9 ko backgroundĪctivation reactions are highly amplifying We begin by a brief introduction to the activation and deactivation steps in phototransduction and then focus on the quantitative physiological measures that provide kinetic insights into the biochemical events underlying response recovery in living photoreceptors, as exemplified by mouse rods.įaster kinetics - diffusion and volume effects
The goal of this review is to summarize recent findings in the deactivation of this prototypical G-protein cascade and to articulate several remaining questions. Many lines of mice in which phototransduction proteins have been knocked out or mutated have been characterized physiologically some of these are given in Table 1. With the adaptation of suction electrode recording to mouse rods in the mid-1990s in Denis Baylor’s laboratory, it became feasible to assess how the photoresponse is affected by deletions, mutations, and transgenic overexpression of proteins thought to regulate the cascade.
The understanding of the molecular basis of phototransduction and its regulation has greatly expanded with the application of mouse gene-targeting techniques, which made it possible to knock out or otherwise perturb the phototransduction machinery of intact photoreceptors.
The absorption of photons by the G-protein-coupled receptor (GPCR), rhodopsin, in the outer segments of retinal rod photoreceptors activates a series of biochemical reactions, called the phototransduction cascade, which generates the electrical response to light and thus mediates the first steps in vision.