CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory.

Protein phosphorylation is an essential step for the expression of long-term potentiation (LTP), a long-lasting, activity-dependent strengthening of synaptic transmission widely regarded as a cellular mechanism underlying learning and memory. At the core of LTP is the synaptic insertion of AMPA receptors (AMPARs) triggered by the NMDA receptor-dependent activation of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII). However, the CaMKII substrate that increases AMPAR-mediated transmission during LTP remains elusive. Here, we identify the hippocampus-enriched but not as a critical CaMKII substrate for LTP. We found that LTP induction increases phosphorylation, and that CaMKII-dependent enhancement of AMPAR-mediated transmission requires CaMKII phosphorylation sites of Moreover, LTP and memory formation, but not basal transmission, are significantly impaired in mice lacking CaMKII phosphorylation sites of Tduanyu37γ-8. Together, these findings demonstrate that Tduanyu37γ-8 is a crucial mediator of CaMKII-dependent LTP and therefore a molecular target that controls synaptic plasticity and associated cognitive functions.

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