Normal brain development and developmental neurological diseases involve important cellular signal transduction phenomena that are poorly understood. Protein methylation is a relatively novel signal transduction mechanism likely to play a role in the development of neuronal cells. This research application is intended to elucidate the means by which this post-translational modification influences the promotion of neurite outgrowth from neuronal cells.
The specific aims are:
Aim 1 : Determine which NGF-activated signaling pathways lead to increased activity of type I protein arginine methyl transferases (PRMTs). This will be accomplished by comparison of NGF receptor mutants with wildtype cells.
Aim 2 will directly assess the roles of two specific PRMTs (PRMT 1 and 3) in neurite outgrowth by molecular biological, biochemical and immunological techniques.
Aim 3 is designed to establish a role for protein arginine methylation in the regulation of process outgrowth from NGF-responsive neurons. Elements of the procedures and methods utilized in Aims 1 and 2 will be adapted to the experiments of this aim utilizing primary cultures of sympathetic and dorsal root ganglia neurons.
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