Growth factor receptor-bound protein 14 undergoes light-dependent intracellular translocation in rod photoreceptors: functional role in retinal insulin receptor activation.
Growth factor receptor-bound protein 14 (Grb14) is involved in growth factor receptor tyrosine kinase signaling. Here we report that light causes a major redistribution of Grb14 among the individual subcellular compartments of the retinal rod photoreceptor. Grb14 is localized predominantly to the inner segment, nuclear layer, and synapse in dark-adapted rods, whereas in the light-adapted rods, Grb14 redistributed throughout the entire cell, including the outer segment. The translocation of Grb14 requires photoactivation of rhodopsin, but not signaling through the phototransduction cascade, and is not based on direct Grb14-rhodopsin interactions. We previously hypothesized that Grb14 protects light-dependent insulin receptor (IR) activation in rod photoreceptors against dephosphorylation by protein tyrosine phosphatase 1B. Consistent with this hypothesis, we failed to observe light-dependent IR activation in Grb14(-/-) mouse retinas. Our studies suggest that Grb14 translocates to photoreceptor outer segments after photobleaching of rhodopsin and protects IR phosphorylation in rod photoreceptor cells. These results demonstrate that Grb14 can undergo subcellular redistribution upon illumination and suggest that rhodopsin photoexcitation may trigger signaling events alternative to the classical transducin activation.
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma73104, USA.
Ammaji
A
Rajala
Roger J
RJ
Daly
Masaki
M
Tanito
Dustin T
DT
Allen
Lowenna J
LJ
Holt
Ekaterina S
ES
Lobanova
Vadim Y
VY
Arshavsky
Raju V S
RV
Rajala
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008027:Light; D055537:Light Signal Transduction; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D012374:Rod Cell Outer Segment / Q000378:metabolism; D015398:Signal Transduction; D015293:Transducin / Q000235:genetics / Q000378:metabolism; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005136:Eye Proteins; D011506:Proteins; D011972:Receptor, Insulin; D015293:Transducin; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C490977:Grb14 protein, mouse