Abstract
Recent years have witnessed a revolution in our understanding of signaling in neuronal compartments and the manifold functions of a variety of stimulations that regulate protein translation locally. Glutamate is the principal excitatory neurotransmitter in mammalian CNS and also acts as a cue guiding axonal and neuronal migration during the early phase of development. In this study, we found that glutamate stimulates axonal translation by binding to AMPA receptors and metabotropic glutamate receptors and activating Ca2+ influx and the mTOR signaling. These data demonstrate that glutamate-induced stimulation of local translation may partake in regulating axonal functions during development. The dependencies of axonal translation on neuronal types and stimulating reagents have also been studied here. Our results suggest that local translation can be activated by glutamate, BDNF, Netrin-1, and semaphorin 3A stimulation in cortical axons but not in hippocampal ones. Furthermore, Netrin-1- or semaphorin 3A-induced enhancements of translation are mediated by pathways different from those mediating the BDNF- or glutamate-induced enhancements of translation in cortical axons. Taken together, our finding from this thesis implies the mechanisms underlying axonal translation depend on they neuronal types as well as on the nature of stimulation reagents.