Insulin receptor signaling regulates actin cytoskeletal organization in developing photoreceptors |
| |
Authors: | Raju V S Rajala†‡ Ammaji Rajala‡ Richard S Brush‡ Nora P Rotstein§ Luis E Politi§ |
| |
Institution: | Departments of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Dean A. McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Instituto de Investigaciones Bioquímicas (INIBIBB), CONICET and Universidad Nacional del Sur, Bahía Blanca, Argentina |
| |
Abstract: | The insulin receptor (IR) and IR signaling proteins are widely distributed throughout the CNS. IR signaling provides a trophic signal for transformed retinal neurons in culture and we recently reported that deletion of IR in rod photoreceptors by Cre/ lox system resulted in stress-induced photoreceptor degeneration. These studies suggest a neuroprotective role of IR in rod photoreceptor cell function. However, there are no studies available on the role of insulin-induced IR signaling in the development of normal photoreceptors. To examine the role of insulin-induced IR signaling, we analyzed cultured neuronal cells isolated from newborn rodent retinas. In insulin-lacking cultures, photoreceptors from wild-type rat retinas exhibited an abnormal morphology with a wide axon cone and disorganization of the actin and tubulin cytoskeleton. Photoreceptors from IR knockout mouse retinas also exhibited a similar abnormal morphology. A novel finding in this study was that addition of docosahexaenoic acid, a photoreceptor trophic factor, restored normal axonal outgrowth in insulin-lacking cultures. These data suggest that IR signaling pathways regulate actin and tubulin cytoskeletal organization in photoreceptors; they also imply that insulin and docosahexaenoic acid activate at least partially overlapping signaling pathways that are essential for the development of normal photoreceptors. |
| |
Keywords: | differentiation docosahexaenoic acid insulin insulin receptors neurite outgrowth neuron survival photoreceptors retina |
|
|