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

26 Citations (Scopus)

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

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
Long-Term Memory
Long-Term Potentiation
Phosphorylation
Learning
AMPA Receptors
Neuronal Plasticity
TARP
N-Methyl-D-Aspartate Receptors
Synaptic Transmission
Cognition
Hippocampus

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Park, J., Chávez, A. E., Mineur, Y. S., Morimoto-Tomita, M., Lutzu, S., Kim, K. S., ... 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

CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory. / Park, Joongkyu; Chávez, Andrés E.; Mineur, Yann S.; Morimoto-Tomita, Megumi; Lutzu, Stefano; Kim, Kwang S.; Picciotto, Marina R.; Castillo, Pablo E.; Tomita, Susumu.

In: Neuron, Vol. 92, No. 1, 05.10.2016, p. 75-83.

Research output: Contribution to journalArticle

Park, J, Chávez, AE, Mineur, YS, Morimoto-Tomita, M, Lutzu, S, Kim, KS, Picciotto, MR, Castillo, PE & Tomita, S 2016, 'CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory', Neuron, vol. 92, no. 1, pp. 75-83. https://doi.org/10.1016/j.neuron.2016.09.002
Park J, Chávez AE, Mineur YS, Morimoto-Tomita M, Lutzu S, Kim KS et al. CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory. Neuron. 2016 Oct 5;92(1):75-83. https://doi.org/10.1016/j.neuron.2016.09.002
Park, Joongkyu ; Chávez, Andrés E. ; Mineur, Yann S. ; Morimoto-Tomita, Megumi ; Lutzu, Stefano ; Kim, Kwang S. ; Picciotto, Marina R. ; Castillo, Pablo E. ; Tomita, Susumu. / CaMKII Phosphorylation of TARPγ-8 Is a Mediator of LTP and Learning and Memory. In: Neuron. 2016 ; Vol. 92, No. 1. pp. 75-83.
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