| First Author | Park J | Year | 2016 |
| Journal | Neuron | Volume | 92 |
| Issue | 1 | Pages | 75-83 |
| PubMed ID | 27667007 | Mgi Jnum | J:253355 |
| Mgi Id | MGI:6109601 | Doi | 10.1016/j.neuron.2016.09.002 |
| Citation | Park J, et al. (2016) CaMKII Phosphorylation of TARPgamma-8 Is a Mediator of LTP and Learning and Memory. Neuron 92(1):75-83 |
| abstractText | 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 Ca(2+)/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 TARPgamma-8, but not TARPgamma-2/3/4, as a critical CaMKII substrate for LTP. We found that LTP induction increases TARPgamma-8 phosphorylation, and that CaMKII-dependent enhancement of AMPAR-mediated transmission requires CaMKII phosphorylation sites of TARPgamma-8. Moreover, LTP and memory formation, but not basal transmission, are significantly impaired in mice lacking CaMKII phosphorylation sites of TARPgamma-8. Together, these findings demonstrate that TARPgamma-8 is a crucial mediator of CaMKII-dependent LTP and therefore a molecular target that controls synaptic plasticity and associated cognitive functions. |
