Copine 6, a novel calcium sensor translating synaptic activity into spine plasticity : or, "Copine 6 a brainsporter in action"

Changes in synaptic activity alter synaptic transmission, ultimatively changing neuronal network dynamics. Importantly, shifting synaptic properties often induces calcium-dependent structural rearrangements. The consequence of activity-dependent influx of calcium has been well studies and many of its targets have emerged over the last years. However, most of these studies are emphasizing the interaction of these proteins but ignore mechanisms controlling its spatio-temporal properties. Here we introduce a novel mechanism for activity dependent synapse plasticity based on protein translocation. We were able to demonstrate increased synaptic activity upon loss of Copine 6 in hippocampal neurons and show its enrichment in postsynaptic compartments upon NMDA receptor dependent calcium influx. Moreover, we show evidence for Copine 6 acting as a shuttle protein for the small Rho-like GTPase Rac1. In the presence of Copine 6, Rac1 shows calcium dependent enrichment at cell membranes. Interestingly neurons expressing a calcium-insensitive version of Copine 6 lose active synapses. Together, these data provide evidence that Copine 6 translates synaptic activity into morphological changes trough translocation of Rac1 into synaptic structures in a calcium-dependent manner.