1. CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory.
- Author
-
Park J, Chávez AE, Mineur YS, Morimoto-Tomita M, Lutzu S, Kim KS, Picciotto MR, Castillo PE, and Tomita S
- Subjects
- Animals, Calcium Channels genetics, Calcium-Calmodulin-Dependent Protein Kinase Type 2 genetics, Hippocampus metabolism, Mice, Mice, Knockout, Phosphorylation, Receptors, AMPA metabolism, Calcium Channels metabolism, Calcium-Calmodulin-Dependent Protein Kinase Type 2 physiology, Learning physiology, Long-Term Potentiation physiology, Memory physiology
- Abstract
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 TARPγ-8, but not TARPγ-2/3/4, as a critical CaMKII substrate for LTP. We found that LTP induction increases TARPγ-8 phosphorylation, and that CaMKII-dependent enhancement of AMPAR-mediated transmission requires CaMKII phosphorylation sites of TARPγ-8. Moreover, LTP and memory formation, but not basal transmission, are significantly impaired in mice lacking CaMKII phosphorylation sites of TARPγ-8. Together, these findings demonstrate that TARPγ-8 is a crucial mediator of CaMKII-dependent LTP and therefore a molecular target that controls synaptic plasticity and associated cognitive functions., (Copyright © 2016 Elsevier Inc. All rights reserved.)- Published
- 2016
- Full Text
- View/download PDF