Insulin receptor signaling regulates actin cytoskeletal organization in developing photoreceptors.
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.
Rajala
Raju V S
RV
Departments of Ophthalmology, University of Oklahoma Health Sciences Center, 608 Stanton L. Young Blvd., Oklahoma City, OK 73104, USA. raju-rajala@ouhsc.edu
Rajala
Ammaji
A
Brush
Richard S
RS
Rotstein
Nora P
NP
Politi
Luis E
LE
D000199:Actins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D010786:Photoreceptor Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics
D000199:Actins; D011972:Receptor, Insulin