First Author | Rajala RV | Year | 2009 |
Journal | J Neurochem | Volume | 110 |
Issue | 5 | Pages | 1648-60 |
PubMed ID | 19575708 | Mgi Jnum | J:152239 |
Mgi Id | MGI:4357716 | Doi | 10.1111/j.1471-4159.2009.06262.x |
Citation | Rajala RV, et al. (2009) Insulin receptor signaling regulates actin cytoskeletal organization in developing photoreceptors. J Neurochem 110(5):1648-60 |
abstractText | 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. |