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Cited by 121Neuroscience and Neuropharmacology ResearchMemory and Neural MechanismsGenetics and Neurodevelopmental Disorders

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

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Park, Joongkyu, Chávez, Andrés E., Mineur, Yann S., Morimoto-Tomita, Megumi, Lutzu, Stefano, Kim, Kwang S., Picciotto, Marina R., Castillo, Pablo E. +1 more·2016·Neuron
DOI 10.1016/j.neuron.2016.09.002PMC PMC5059846
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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.

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  • CaMKII phosphorylation of TARP serines neutralizes charge, releasing the CTD and providing access to the PDZ domains of PSD-95.

    “CaMKII phosphorylation of the serines neutralizes the charge, releasing the CTD and providing access to the PDZ domains of PSD-95 (284, 285, 287).”

    From Synaptic memory and CaMKII (2023) · cites this paper as [284]

    The Results section identifies TARPγ-8 serines phosphorylated by CaMKIIα. The Discussion describes phosphorylation-related electrostatic changes releasing the cytoplasmic domain from membrane lipids and enabling PSD-95 interaction, but specifically for TARPγ-2. It does not establish that CaMKII phosphorylation of TARPγ-8 neutralizes charge and exposes its PSD-95-binding site. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Two key CaMKII phosphorylation sites on TARP γ-8, S277 and S281, are important mediators of hippocampal LTP and learning and memory.

    “A recent study that used knock-in mutations demonstrated that two key CaMKII phosphorylation sites on TARP γ-8, S277 and S281, are important mediators of hippocampal LTP and learning and memory (Park et al., 2016).”

    From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Park et al., 2016

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Cited by

Sorted by citations

Authors
Park, J., Chávez, A. E., Mineur, Y. S., Morimoto-Tomita, M., Lutzu, S., Kim, K. S., Picciotto, M. R., Castillo, P. E., & Tomita, S.
Affiliations
  • Yale University (US)
  • Albert Einstein College of Medicine (US)
Corresponding author
  • Castillo, Pablo E.
  • Tomita, Susumu
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2016-10
Volume
92
Issue
1
Pages
75-83
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2016.09.002
PMC
PMC5059846
OpenAlex
W2521766521
Cited by
121
References
9
Citations by year
2026: 8 · 2025: 7 · 2024: 17 · 2023: 11 · 2022: 13 · 2021: 21 · 2020: 12 · 2019: 7 · 2018: 15 · 2017: 9 · 2016: 1
FWCI
4.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Yale University
  • National Institutes of Health (UL1TR001863)
  • National Institute of Mental Health (R03MH105824, R01MH081935, R01MH077939, R01MH077681, R56MH077939)
  • National Institute on Drug Abuse (R01DA014241, R01DA017392, P30DA018343, R37DA014241)
  • National Institute of Neurological Disorders and Stroke (U24NS050606)
  • National Center for Advancing Translational Sciences
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords
CaMKII, Stargazer, protein phosphorylation, long-term potentiation, synaptic plasticity, learning and memory, hippocampus, NMDA receptor, synaptic transmission
MeSH terms
Animals, Hippocampus, Learning, Memory, Phosphorylation, Calcium Channels, Long-Term Potentiation, Receptors, AMPA, Mice, Knockout, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2

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