DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific

Dayton J. Goodell, Vincent Zaegel, Steven J. Coultrap, Johannes W Hell, K. Ulrich Bayer

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP. We find that the LTP specificity of CaMKII synaptic accumulation is due to its LTD-specific suppression by calcineurin (CaN)-dependent DAPK1 activation, which in turn blocks CaMKII binding to GluN2B. This suppression is enabled by competitive DAPK1 versus CaMKII binding to GluN2B. Negative regulation of DAPK1/GluN2B binding by Ca2+/CaM results in synaptic DAPK1 removal during LTP but retention during LTD. A pharmacogenetic approach showed that suppression of CaMKII/GluN2B binding is a DAPK1 function required for LTD.

Original languageEnglish (US)
Pages (from-to)2231-2243
Number of pages13
JournalCell Reports
Volume19
Issue number11
DOIs
StatePublished - Jun 13 2017

Fingerprint

Death-Associated Protein Kinases
Long-Term Potentiation
Protein Kinases
Depression
Neuronal Plasticity
Plasticity
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcineurin
Pharmacogenetics
Cell death
Calmodulin
N-Methyl-D-Aspartate Receptors
Cognition
Cell Death
Chemical activation
Learning
Data storage equipment

Keywords

  • calcineurin
  • CaMKII
  • DAPK1
  • death-associated protein kinase
  • dendritic spine
  • GluN2B
  • hippocampus
  • LTD
  • LTP
  • synapse

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Goodell, D. J., Zaegel, V., Coultrap, S. J., Hell, J. W., & Bayer, K. U. (2017). DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific. Cell Reports, 19(11), 2231-2243. https://doi.org/10.1016/j.celrep.2017.05.068

DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific. / Goodell, Dayton J.; Zaegel, Vincent; Coultrap, Steven J.; Hell, Johannes W; Bayer, K. Ulrich.

In: Cell Reports, Vol. 19, No. 11, 13.06.2017, p. 2231-2243.

Research output: Contribution to journalArticle

Goodell, DJ, Zaegel, V, Coultrap, SJ, Hell, JW & Bayer, KU 2017, 'DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific', Cell Reports, vol. 19, no. 11, pp. 2231-2243. https://doi.org/10.1016/j.celrep.2017.05.068
Goodell, Dayton J. ; Zaegel, Vincent ; Coultrap, Steven J. ; Hell, Johannes W ; Bayer, K. Ulrich. / DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific. In: Cell Reports. 2017 ; Vol. 19, No. 11. pp. 2231-2243.
@article{88ed13ac07904e75befa95079f06f589,
title = "DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific",
abstract = "The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP. We find that the LTP specificity of CaMKII synaptic accumulation is due to its LTD-specific suppression by calcineurin (CaN)-dependent DAPK1 activation, which in turn blocks CaMKII binding to GluN2B. This suppression is enabled by competitive DAPK1 versus CaMKII binding to GluN2B. Negative regulation of DAPK1/GluN2B binding by Ca2+/CaM results in synaptic DAPK1 removal during LTP but retention during LTD. A pharmacogenetic approach showed that suppression of CaMKII/GluN2B binding is a DAPK1 function required for LTD.",
keywords = "calcineurin, CaMKII, DAPK1, death-associated protein kinase, dendritic spine, GluN2B, hippocampus, LTD, LTP, synapse",
author = "Goodell, {Dayton J.} and Vincent Zaegel and Coultrap, {Steven J.} and Hell, {Johannes W} and Bayer, {K. Ulrich}",
year = "2017",
month = "6",
day = "13",
doi = "10.1016/j.celrep.2017.05.068",
language = "English (US)",
volume = "19",
pages = "2231--2243",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "11",

}

TY - JOUR

T1 - DAPK1 Mediates LTD by Making CaMKII/GluN2B Binding LTP Specific

AU - Goodell, Dayton J.

AU - Zaegel, Vincent

AU - Coultrap, Steven J.

AU - Hell, Johannes W

AU - Bayer, K. Ulrich

PY - 2017/6/13

Y1 - 2017/6/13

N2 - The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP. We find that the LTP specificity of CaMKII synaptic accumulation is due to its LTD-specific suppression by calcineurin (CaN)-dependent DAPK1 activation, which in turn blocks CaMKII binding to GluN2B. This suppression is enabled by competitive DAPK1 versus CaMKII binding to GluN2B. Negative regulation of DAPK1/GluN2B binding by Ca2+/CaM results in synaptic DAPK1 removal during LTP but retention during LTD. A pharmacogenetic approach showed that suppression of CaMKII/GluN2B binding is a DAPK1 function required for LTD.

AB - The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP. We find that the LTP specificity of CaMKII synaptic accumulation is due to its LTD-specific suppression by calcineurin (CaN)-dependent DAPK1 activation, which in turn blocks CaMKII binding to GluN2B. This suppression is enabled by competitive DAPK1 versus CaMKII binding to GluN2B. Negative regulation of DAPK1/GluN2B binding by Ca2+/CaM results in synaptic DAPK1 removal during LTP but retention during LTD. A pharmacogenetic approach showed that suppression of CaMKII/GluN2B binding is a DAPK1 function required for LTD.

KW - calcineurin

KW - CaMKII

KW - DAPK1

KW - death-associated protein kinase

KW - dendritic spine

KW - GluN2B

KW - hippocampus

KW - LTD

KW - LTP

KW - synapse

UR - http://www.scopus.com/inward/record.url?scp=85020708726&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020708726&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2017.05.068

DO - 10.1016/j.celrep.2017.05.068

M3 - Article

C2 - 28614711

AN - SCOPUS:85020708726

VL - 19

SP - 2231

EP - 2243

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 11

ER -