Activity dependent remodeling of synaptic connections is important for the precise wiring of the developing central nervous system, learning and memory, as well as re-routing neural circuitry after trauma. Thus, understanding the molecular mechanisms underlying this process will broaden our insight into the developing as well as the mature brain, and may ultimately contribute to the development of therapeutic treatments for neural trauma. The recent findings that MHC class I, beta2-m, and CD3zeta play a role in synaptic remodeling suggests that signaling and adhesion mechanisms known to mediate cell-cell interactions in the immune system, have a function in the central nervous system as well. We will characterize the subcellular localization of these proteins in the mammalian visual system and hippocampus using biochemical fractionation, immunofluorescence microscopy, and immunoelectron microscopy. We will test the function of these proteins in an in vitro synapse formation system. We will also identify and characterize candidate and novel proteins that may cooperate with MHC class I, beta2- m and CD3zeta in the central nervous system using cDNA arrays, in situ hybridization, and co-immunoprecipitation techniques. Results of these studies should broaden our understanding of the molecular mechanisms of synapse formation and use-dependent stabilization.
| Syken, Josh; Shatz, Carla J (2003) Expression of T cell receptor beta locus in central nervous system neurons. Proc Natl Acad Sci U S A 100:13048-53 |
