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- Title
Insulin receptor signaling regulates actin cytoskeletal organization in developing photoreceptors.
- Authors
Rajala, Raju V. S.; Rajala, Ammaji; Brush, Richard S.; Rotstein, Nora P.; Politi, Luis E.
- 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.
- Subjects
DOCOSAHEXAENOIC acid; INSULIN; PHOTORECEPTORS; RETINA; TUBULINS; NEUROPROTECTIVE agents
- Publication
Journal of Neurochemistry, 2009, Vol 110, Issue 5, p1648
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2009.06262.x