Light regulation of the insulin receptor in the retina.
The peptide hormone insulin binds its cognate cell-surface receptors to activate a coordinated biochemical-signaling network and to induce intracellular events. The retina is an integral part of the central nervous system and is known to contain insulin receptors, although their function is unknown. This article, describes recent studies that link the photobleaching of rhodopsin to tyrosine phosphorylation of the insulin receptor and subsequent activation of phosphoinositide 3- kinase (PI3K). We recently found a light-dependent increase in tyrosine phosphorylation of the insulin receptor-beta-subunit (IR beta) and an increase in PI3K enzyme activity in isolated rod outer segments (ROS) and in anti-phosphotyrosine (PY) and anti-IR beta immunoprecipitates of retinal homogenates. The light effect, which was localized to photoreceptor neurons, is independent of insulin secretion. Our results suggest that light induces tyrosine phosphorylation of IR beta in outer-segment membranes, which leads to the binding of p85 through its N-terminal SH2 domain and the generation of PI-3,4,5-P3. We suggest that the physiological role of this process may be to provide neuroprotection of the retina against light damage by activating proteins that protect against stress-induced apoptosis. The studies linking PI3K activation through tyrosine phosphorylation of IR beta now provide physiological relevance for the presence of these receptors in the retina.
Rajala
Raju V S
RV
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, USA. raju-rajala@ouhsc.edu
Anderson
Robert E
RE
D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D010775:Photic Stimulation / Q000009:adverse effects; D011972:Receptor, Insulin / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000166:cytology / Q000201:enzymology*; D013312:Stress, Physiological / Q000201:enzymology / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism*
D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin