Brain function is defined by specific connections or synapses through which nerve cells communicate with each other. This activity depends on the assembly of specific molecular components on both sides of the synapse. Modulation of synaptic structure and signaling strength appears to be fundamentally important to the higher order processes of learning and memory. Recent work has revealed that synaptic function may be regulated by targeted protein degradation. Expression of the E3 ubiquitin ligase RPM-1, a proposed component of the protein degradation machinery, is required for normal synaptic morphology in the nematode, C. elegans. Genetic experiments have revealed that rpm-1 negatively regulates a MAP kinase signaling cascade. My research has shown that rpm-1 also controls expression of neuronal genes. As MAP kinase components are known to modulate synaptic plasticity through transcriptional regulation, I propose that this rpm-1 dependent pathway regulates specific genes involved in synapse formation. A collection of rpm-1 like mutants that I have isolated will be characterized to identify key components of this pathway. New and powerful microarray technology developed in this laboratory will be employed to identify rpm-1 regulated genes. Bona fide rpm-1 regulated genes will be tested genetically for roles in synapse formation and stabilization. This work should reveal genes involved in synaptogenesis. ? ?
