Comparative expression profiles of Trk receptors and Shc-related phosphotyrosine adapters during retinal development: potential roles of N-Shc/ShcC in brain-derived neurotrophic factor signal transduction and modulation.

摘要

Neurotrophins (NTs) have multiple roles in retinal development and survival, which are mediated through their specific receptors and signaling molecules. An emerging family of adapter protein, Shc (Src homology and collagen)-related molecules, i.e., Shc/ShcA, Sck/ShcB, and N-Shc/ShcC, has been implicated in various phosphotyrosine signal transduction mechanisms, including that for NTs. To explore the potential role(s) of Shc-related adapters in NT signaling in the retina, we compared the developmental changes of the mRNA expression of TrkA -B, and -C in the rat retina, on one hand and, on the other hand, studied which members of the Shc family were activated after brain-derived neurotrophic factor (BDNF) application in axotomized rat retinas. Early in development, both TrkA and ShcA were highly expressed, whereas, in late development to adulthood, TrkB/C and ShcB/C were highly expressed. In the mature retinal ganglion cell layer, the expression of ShcB/C and TrkB/C was evident. Immunoreactivity of ShcC was located in the retinal ganglion cells, amacrine cells, and inner plexiform layer. The response of ShcC following retinal axotomy was most profound with the administration of BDNF, and there was some response with neurotrophin-3. These results indicate that ShcC could be a potential phosphotyrosine adapter among the Shc family members for BDNF signaling and function during retinal development and regeneration in vivo.