Insulin receptor signaling regulates actin cytoskeletal organization in developing photoreceptors

RAJALA, RVS., RAJALA,A., BRUSH ,R ; ROTSTEIN,NP., AND POLITI. LE

JOURNAL OF NEUROCHEMISTRY

Blackwell Science

Año: 2009 vol. 110 p. 1648 - 1660

0022-3042

The insulin receptor (IR) and IR signaling proteins are widelydistributed throughout the CNS. IR signaling provides atrophic signal for transformed retinal neurons in culture andwe recently reported that deletion of IR in rod photoreceptorsby Cre/lox system resulted in stress-induced photoreceptordegeneration. These studies suggest a neuroprotective role ofIR in rod photoreceptor cell function. However, there are nostudies available on the role of insulin-induced IR signaling inthe development of normal photoreceptors. To examine therole of insulin-induced IR signaling, we analyzed culturedneuronal cells isolated from newborn rodent retinas. In insulinlackingcultures, photoreceptors from wild-type rat retinasexhibited an abnormal morphology with a wide axon cone anddisorganization of the actin and tubulin cytoskeleton. Photoreceptorsfrom IR knockout mouse retinas also exhibited asimilar abnormal morphology. A novel finding in this studywas that addition of docosahexaenoic acid, a photoreceptortrophic factor, restored normal axonal outgrowth in insulinlackingcultures. These data suggest that IR signaling pathwaysregulate actin and tubulin cytoskeletal organization in photoreceptors;they also imply that insulin and docosahexaenoic acidactivate at least partially overlapping signalingpathwaysthat areessential for the development of normal photoreceptors