Wrd promotes active zone stability through dephosphorylation of Coracle

Lsu Health Sciences Center, New Orleans LA

Investigators

Abstract

Wrd promotes active zone stability through dephosphorylation of Coracle Abstract Active zones (AZs) are specialized membrane compartments at the nerve terminal that orchestrate the release of neurotransmitters. AZs are structurally plastic as their number, size, location and strength can each be dynamically modified by developmental cues and neural activities. This form of structural neuroplasticity may play key roles in learning and memory, and its dysfunction may cause cognitive impairment. However, we know very little about the molecular mechanisms that regulate AZ scaffold dynamics. We found that synaptic PP2A/Wrd phosphatase promotes AZ stability at the Drosophila NMJs, and is required for light-induced AZ remodeling at the photoreceptor synapses and taste learning at the adult stage. Through a comparative proteomic approach, we identified Coracle (Cora, mammalian homologue is called protein 4.1), a hub protein that organizes intercellular junctions and membrane proteins, as a key Wrd-specific substrate that could mediate the AZ scaffold dynamics. This proposal addresses the following two questions: First, what are the roles of Coracle in synaptic development and stabilization? Second, how does the dephosphorylation of Coracle by Wrd/PP2A alter the action of Coracle at the presynaptic terminal? In Aim 1, we will define a novel role of synaptically localized Cora in regulating AZ dynamics at the developing and mature synapses, as well as learning and memory. In Aim 2, we will define how Wrd-mediated dephosphorylation of Cora affects Cora-mediated action in regulating synaptic stability and cognitive function.