II. Molecular Basis of Vision

C. Signaling pathway of phototransduction

The initial, light-triggered events in phototransduction occur on the outer segment membranes of rod and cone photoreceptors. The signaling pathway for visual excitation in rods represents a prototypical G-protein cascade comprising the seven-transmembrane receptor (rhodopsin), the heterot rimeric G-protein (transducin), and the effector (phosphodiesterase; PDE). Photo-isomerization of 11-cis retinal bound to rhodopsin activates transducin by accelerating guanine nucleotide exchange on its αt subunit to form αt*-GTP; this step represents one stage of amplification of the light signal, since activated rhodopsin acts catalytically on many transducin molecules. Each αt*-GTP can bind to PDE to relieve the inhibitory constraint on its hydrolytic activity, thereby causing a rapid decline in the cytoplasmic cGMP levels in the outer segment of the rod photoreceptor cell. The high rates of cGMP hydrolysis by each activated PDE create a second stage of signal amplification. Cyclic nucleotide-gated ion channels in the plasma membrane of the outer segment respond to this drop in cGMP by closing, resulting in membrane hyperpolarization and producing the electrical response of the cell.

Much has been learned about the excitation mechanism of visual transduction in the rod outer segment (ROS), including:
(1) a detailed biochemical model that correlates well with the initial rising phase of the electrical response to light (Pugh and Lamb, 2000);
(2) high-resolution structures of the rhodopsin (Palczewski et al., 2000) and transducin (Sondek et al., 1994) molecules;
(3) descriptions of the activation mechanism of PDE (Arshavsky et al., 2002; Cote, 2003), and;
(4) regulation of the the cyclic nucleotide-regulated ion channel by cGMP and other modulators (Molday and Kaupp, 2000).

References

Arshavsky,V.Y., Lamb,T.D., and Pugh,E.N., Jr. (2002). G proteins and phototransduction. Annu. Rev. Physiol. 64, 153-187.

Cote,R.H. (2003). Structure, function, and regulation of photoreceptor phosphodiesterase (PDE6). In Handbook of Cell Signaling, R.A.Bradshaw and

Molday,R.S. and Kaupp,U.B. (2000). Ion channels of vertebrate photoreceptors. In Molecular Mechanisms in Visual Transduction, D.G.Stavenga, W.J.DeGrip, and E.N.Pugh, Jr., eds. (Amsterdam: North Holland), pp. 143-181.

Palczewski,K., Kumasaka,T., Hori,T., Behnke,C.A., Motoshima,H., Fox,B.A., Le Trong,I., Teller,D.C., Okada,T., Stenkamp,R.E., Yamamoto,M., and Miyano,M. (2000). Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289, 739-745.

Pugh,E.N. and Lamb,T.D. (2000). Phototransduction in vertebrate rods and cones: molecular mechanisms of amplification, recovery and light adaptation. In Molecular Mechanisms in Visual Transduction, D.G.Stavenga, W.J.DeGrip, and E.N.Pugh, eds. (New York: Elsevier Science B.V.), pp. 183-255.

Sondek,J., Lambright,D.G., Noel,J.P., Hamm,H.E., and Sigler,P.B. (1994). GTPase mechanism of G-proteins from the 1.7-Å crystal structure of transducin α-GDP-AlF4-. Nature 372, 276-279.