Abstract
Purpose: :
To investigate the hypothesis that Arrestin1 (Arr1, "rod arrestin") is responsible for the differential inactivation kinetics of UV– and M–cone pigment driven responses of Nrl–/– Grk1–/– mouse cone photoreceptors. Photoreceptors of the Nrl–/– mouse have been classified as cones on the basis of morphological, molecular, and electrophysiological criteria1. Like WT mouse cones, Nrl–/– photoreceptors functionally co–express both short (S–) and mid (M–) wavelength sensitive cone opsins2 and a single GRK, Grk1. In individual cones of Nrl–/– Grk1–/– mice, UV–opsin driven responses inactivate much more rapidly than M–opsin driven responses2. A plausible hypothesis that could explain this differential inactivation is that photoactivated, unphosphorylated UV–opsin can be inactivated by Arr1, which is co–expressed with cone arrestin in Nrl–/– and WT mouse cone photoreceptors 3,4.
Methods: :
Responses of single cones of Nrl–/– Grk1–/– and Nrl–/– Grk1–/– Arr–/– mice to brief flashes of light were measured with suction pipette recordings. The times to 50% recovery (ΔT50) of dim flash responses to UV and mid–wave light were measured and compared.
Results: :
The ΔT50 of M–opsin driven responses of photoreceptors of both Nrl–/– Grk1–/– and Nrl–/– Grk1–/– Arr–/– mice was on average ∼3 – fold longer than that for the UV–opsin driven responses. Responses of cones of either genotype to UV– or mid–wavelength flashes had similar kinetics.
Conclusions: :
The hypothesis that Arr1 or any splice variant of Arr1 is responsible for the differential inactivation kinetics of UV– and M–cone opsins in the absence of GRK1 is rejected. Other hypotheses are under active consideration. 1L. L. Daniele et al., IOVS 46, 2156–2167 (2005). 2 S. S. Nikonov et al., J Gen Physiol 125, 287–304 (2005). 3 A. J. Mears et al., Nature Genetics 29, 447–452 (2001). 4 X. Zhu et al., IOVS 2005 46: E–Abstract 1179.
Keywords: opsins • phosphorylation • photoreceptors