Identification of Altered Phosphorylation Signalling in Neurotransmission

Overview: We have identified TARPg-8 as a critical CaMKII substrate for LTP (Park et al., 2016 Neuron). Since then, we have been working on the stoichiometry of TARPg-8 phosphorylation. We identified ten phosphorylation sites in TARPg-8. Among them, CaMKII phosphorylates two sites, and several sites are phosphorylated by PKC, while unidentified kinases phosphorylate remaining four sites. Since combinations of these phosphorylation sites are enormous, we focused on identifying functional phosphorylation sites by measuring synaptic activity in neurons expressing TARPg-8 mutants and identified minimum sets of phosphorylation sites for potentiating synaptic activity. We now identified phosphorylated sites in neurons. Because TARP phosphorylation plays a crucial role in synaptic plasticity also observed during addiction, this study will reveal how addiction is formed through synaptic plasticity and TARP phosphorylated at multiple sites.