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C. M. Krispel, W. W. Rubin, C.-K. Chen, M. E. Burns; Acceleration of Rhodopsin Deactivation in Intact Mouse Rods. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2844.
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Previous studies in rod photoreceptors have shown that overexpression of the RGS9 complex speeds flash response recovery, whereas overexpression of rhodopsin kinase (GRK1) has no effect on flash responses. Because cone opsin kinase (GRK7) is thought to have higher catalytic activity than GRK1, possibly as a result of its C-terminal isoprenyl group (geranylgeranyl, rather than farnesyl as in GRK1), we sought to determine whether overexpression of a geranyl-geranylated GRK1 could accelerate rhodopsin deactivation and thus affect flash responses of transgenic rods.
We created a mutated form of mouse GRK1 that substituted a leucine for the serine at position 561 (RKS561L), which directs the attachment of a geranylgeranyl group, rather than the usual farnesyl group, to the C-terminus of GRK1. The transgene was expressed in rod photoreceptors under the control of the rhodopsin promoter and its function was examined in single rods using suction electrode recordings.
In the GRK1-/- background, RKS561L expression rescued timely recovery of the photoresponse. When expressed on the wildtype background, RKS561L reduced the rod’s sensitivity to light and sped the time course of dim flash responses, unlike the over-expression of GRK1. Unlike the over-expression of RGS9, RKS561L expression did not significantly speed the dominant time constant of recovery of responses to bright flashes.
These results suggest that the identity of the isoprenyl groups of GRKs can dramatically alter the rate at which light-activated opsin is deactivated, possibly by increasing the concentration of GRK located on the disc membrane. These results also further support the notion that the dominant time constant of recovery is set by transducin deactivation, rather than rhodopsin deactivation, in normal rods.
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