After the dark-adapted animals were exposed to light, the transducin α-subunit rapidly translocates from the outer segments to the inner segments of rod photoreceptors, and arrestin translocates from the inner segments to the outer segments. This light-driven massive protein translocation is believed to be an important aspect of tuning photoreceptor sensitivity to various light intensities.
30 Recent studies have suggested that RPE may play important roles in this translocation. In RPE65 knockout mice, which lack the retinoid isomerase needed to convert all-
trans retinyl ester to 11-
cis retinol for rhodopsin activation, the translocation of the transducin α-subunit and arrestin is blocked.
31 We surmised that defects in α1β1 integrin function in retinal pigment epithelial cells may influence protein translocation. We compared protein translocation in integrin α1-null mice with that of age-matched wild-type mice. Four-month-old mice (before any signs of retinal degeneration are observed) were dark adapted overnight and exposed to 1500 lux illumination for 1 hour, and the eyes were immediately fixed. Retinal sections were immunostained with antibodies specific for the arrestin or transducin α-subunit.
Figure 6shows that light-induced translocation of arrestin is apparently normal in the integrin α1-null mice
(Figs. 6C 6D 6G 6H) . Conversely, translocation of the transducin α-subunit is markedly delayed in integrin α1-null mice compared with wild-type mice
(Figs. 6A 6B 6E 6F) . In integrin α1-null mice, after dark adaptation for 8 hours, transducin α was found primarily in the rod outer segments
(Fig. 6E) , as in the wild-type mouse
(Fig. 6A) . After 1 hour of light adaptation (1500 lux), transducin α in the wild-type mouse was translocated to the inner segments
(Fig. 6B) . In integrin α1-null mice, however, after 1 hour of light adaptation of the same intensity, the strongest immunostaining of transducin α was still in the outer segments of the rod photoreceptors
(Fig. 6F) , indicating the light-induced translocation of transducin α was delayed. The defect in transducin α-subunit translocation was apparent before photoreceptor cell degeneration was observed. Interestingly, the delay in transducin translocation was more pronounced in the peripheral retina than in the central retina (data not shown). Delayed translocation of transducin α-subunit was observed in integrin α1-null mice at 2, 6, 8, 12, and 15 months of age, and the degree of this delay compared with that of age- and strain-matched wild-type mice was not qualitatively different across these age groups (not shown), suggesting that the protein translocation defect in these animals did not worsen as a function of progressive retinal degeneration. Transducin translocation in the rod photoreceptors of integrin α-null mice was not completely blocked. After longer light adaptation (more than 4 hours), most of the transducin was translocated to the inner parts of rod photoreceptors, as in wild-type mice (data not shown).