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

Joongkyu Park, Andrés E. Chávez, Yann S. Mineur, Megumi Morimoto-Tomita, Stefano Lutzu, Kwang S. Kim, Marina R. Picciotto, Pablo E. Castillo, Susumu Tomita

Research output: Contribution to journalArticle

36 Scopus citations

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 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 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.

Original languageEnglish (US)
Pages (from-to)75-83
Number of pages9
JournalNeuron
Volume92
Issue number1
DOIs
StatePublished - Oct 5 2016

ASJC Scopus subject areas

  • Neuroscience(all)

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    Park, J., Chávez, A. E., Mineur, Y. S., Morimoto-Tomita, M., Lutzu, S., Kim, K. S., Picciotto, M. R., Castillo, P. E., & Tomita, S. (2016). CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory. Neuron, 92(1), 75-83. https://doi.org/10.1016/j.neuron.2016.09.002