Abnormal photoresponses and light-induced apoptosis in rods lacking rhodopsin kinase

Abstract

Phosphorylation is thought to be an essential first step in the prompt deactivation of photoexcited rhodopsin. In vitro, the phosphorylation can be catalyzed either by rhodopsin kinase (RK) or by protein kinase C (PKC). To investigate the specific role of RK, we inactivated both alleles of the RK gene in mice. This eliminated the light-dependent phosphorylation of rhodopsin and caused the single-photon response to become larger and longer lasting than normal. These results demonstrate that RK is required for normal rhodopsin deactivation. When the photon responses of RK؊͞؊ rods did finally turn off, they did so abruptly and stochastically, revealing a first-order backup mechanism for rhodopsin deactivation. The rod outer segments of RK؊͞؊ mice raised in 12-hr cyclic illumination were 50% shorter than those of normal (RK؉͞؉) rods or rods from RK؊͞؊ mice raised in constant darkness. One day of constant light caused the rods in the RK؊͞؊ mouse retina to undergo apoptotic degeneration. Mice lacking RK provide a valuable model for the study of Oguchi disease, a human RK deficiency that causes congenital stationary night blindness.

Why photoreceptors die (and why they don't)

“…The knocking out of either the rhodopsin kinase or arrestin genes had another effect: rods were also especially sensitive to light damage. (25,27) In both mutant strains, the degeneration was spared if the retinas were kept in darkness.…”

“…Once rhodopsin is activated by light it must be turned off, first by phosphorylation by a protein called rhodopsin kinase, and then by the binding to phosphorylated rhodopsin of another protein called arrestin, which sterically inhibits the binding of transducin and further production of T a -GTP. In the two mutants under study, the gene for rhodopsin kinase (25) or arrestin (26) had been knocked out, with the result that rods in both animals showed a much delayed decay of the electrical response (see Fig. 3).…”

Light-Dependent Translocation of Arrestin in the Absence of Rhodopsin Phosphorylation and Transducin Signaling

“…Termination of the light signal requires that light-activated rhodopsin is deactivated by incorporation of multiple phosphates at its C terminus by rhodopsin kinase (RK) (Wilden et al, 1986;Chen et al, 1999a;Mendez et al, 2000) and the subsequent binding of arrestin (Arr). High-affinity arrestin binding to phosphorylated photolyzed rhodopsin prevents its further interaction with transducin (Wilden et al, 1986;Wilden 1995;Xu et al, 1997).…”

Slowed Photoresponse Recovery and Age-Related Degeneration in Cones Lacking Gprotein-Coupled Receptor Kinase 1

“…Animals reared in 12:12 hr cyclic light and bright constant light have similar ERG b-wave amplitude to those of the same genotype raised in total darkness (X. Zhu et al, in preparation), suggesting that the functional decrease and degeneration of the Nrl −/− Grk1 −/− photoreceptors are dependent on age but independent of light under these conditions, in contrast to the light-induced rod degeneration in the Grk1 −/− mouse retina. 7 …”