title: G-protein-coupled receptor rhodopsin regulates the phosphorylation of retinal insulin receptor.
abstract: We have shown previously that phosphoinositide 3-kinase in the retina is activated in vivo through light-induced tyrosine phosphorylation of the insulin receptor (IR). The light effect is localized to photoreceptor neurons and is independent of insulin secretion (Rajala, R. V., McClellan, M. E., Ash, J. D., and Anderson, R. E. (2002) J. Biol. Chem. 277, 43319-43326). These results suggest that there exists a cross-talk between phototransduction and other signal transduction pathways. In this study, we examined the stage of phototransduction that is coupled to the activation of the IR. We studied IR phosphorylation in mice lacking the rod-specific alpha-subunit of transducin to determine if phototransduction events are required for IR activation. To confirm that light-induced tyrosine phosphorylation of the IR is signaled through bleachable rhodopsin, we examined IR activation in retinas from RPE65(-/-) mice that are deficient in opsin chromophore. We observed that IR phosphorylation requires the photobleaching of rhodopsin but not transducin signaling. To determine whether the light-dependent activation of IR is mediated through the rod or cone transduction pathway, we studied the IR activation in mice lacking opsin, a mouse model of pure cone function. No light-dependent activation of the IR was found in the retinas of these mice. We provide evidence for the existence of a light-mediated IR pathway in the retina that is different from the known insulin-mediated pathway in nonneuronal tissues. These results suggest that IR phosphorylation in rod photoreceptors is signaled through the G-protein-coupled receptor rhodopsin. This is the first study demonstrating that rhodopsin can initiate signaling pathway(s) in addition to its classical phototransduction.
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104; Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Ammaji
authors.initials: A
authors.lastname: Rajala
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104; Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Anderson
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104; Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Jian-Xing
authors.initials: JX
authors.lastname: Ma
authors.affiliation: Department of Ophthalmology, New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts 02111.
authors.forename: Janis
authors.initials: J
authors.lastname: Lem
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Muayyad R
authors.initials: MR
authors.lastname: Al-Ubaidi
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104; Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104. Electronic address: raju-rajala@ouhsc.edu.
authors.forename: Raju V S
authors.initials: RVS
authors.lastname: Rajala
mesh_terms: D000818:Animals; D002417:Cattle; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D012243:Rhodopsin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D012243:Rhodopsin; D011972:Receptor, Insulin