Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors

Jian Wang; Shu Hong Liu; Yang Ping Fu; Jerry H. Wang; You Ming Lu

Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors

Jian Wang, Shu Hong Liu, Yang Ping Fu, Jerry H. Wang, You Ming Lu^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

248 Citations (Scopus)

Abstract

CA1 pyramidal neurons degenerate after transient forebrain ischemia, whereas neurons in other regions of the hippocampus remain intact. Here we show that in rat hippocampal CA1 neurons, forebrain ischemia induces the phosphorylation of the N-methyl-D-aspartate (NMDA) receptor 2A subunit at Ser1232 (phospho-Ser1232). Ser1232 phosphorylation is catalyzed by cyclin-dependent kinase 5 (Cdk5). Inhibiting endogenous Cdk5, or perturbing interactions between Cdk5 and NR2A subunits, abolished NR2A phosphorylation at Ser1232 and protected CA1 pyramidal neurons from ischemic insult. Thus, we conclude that modulation of NMDA receptors by Cdk5 is the primary intracellular event underlying the ischemic injury of CA1 pyramidal neurons.

Original language	English
Pages (from-to)	1039-1047
Number of pages	9
Journal	Nature Neuroscience
Volume	6
Issue number	10
Publication status	Published - 1 Oct 2003
Externally published	Yes

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https://hdl.handle.net/1783.1/9490

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@article{1022b496506a467a97cd613741ef4e51,

title = "Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors",

abstract = "CA1 pyramidal neurons degenerate after transient forebrain ischemia, whereas neurons in other regions of the hippocampus remain intact. Here we show that in rat hippocampal CA1 neurons, forebrain ischemia induces the phosphorylation of the N-methyl-D-aspartate (NMDA) receptor 2A subunit at Ser1232 (phospho-Ser1232). Ser1232 phosphorylation is catalyzed by cyclin-dependent kinase 5 (Cdk5). Inhibiting endogenous Cdk5, or perturbing interactions between Cdk5 and NR2A subunits, abolished NR2A phosphorylation at Ser1232 and protected CA1 pyramidal neurons from ischemic insult. Thus, we conclude that modulation of NMDA receptors by Cdk5 is the primary intracellular event underlying the ischemic injury of CA1 pyramidal neurons.",

author = "Jian Wang and Liu, \{Shu Hong\} and Fu, \{Yang Ping\} and Wang, \{Jerry H.\} and Lu, \{You Ming\}",

year = "2003",

month = oct,

day = "1",

language = "English",

volume = "6",

pages = "1039--1047",

journal = "Nature Neuroscience",

issn = "1097-6256",

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TY - JOUR

T1 - Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors

AU - Wang, Jian

AU - Liu, Shu Hong

AU - Fu, Yang Ping

AU - Wang, Jerry H.

AU - Lu, You Ming

PY - 2003/10/1

Y1 - 2003/10/1

N2 - CA1 pyramidal neurons degenerate after transient forebrain ischemia, whereas neurons in other regions of the hippocampus remain intact. Here we show that in rat hippocampal CA1 neurons, forebrain ischemia induces the phosphorylation of the N-methyl-D-aspartate (NMDA) receptor 2A subunit at Ser1232 (phospho-Ser1232). Ser1232 phosphorylation is catalyzed by cyclin-dependent kinase 5 (Cdk5). Inhibiting endogenous Cdk5, or perturbing interactions between Cdk5 and NR2A subunits, abolished NR2A phosphorylation at Ser1232 and protected CA1 pyramidal neurons from ischemic insult. Thus, we conclude that modulation of NMDA receptors by Cdk5 is the primary intracellular event underlying the ischemic injury of CA1 pyramidal neurons.

AB - CA1 pyramidal neurons degenerate after transient forebrain ischemia, whereas neurons in other regions of the hippocampus remain intact. Here we show that in rat hippocampal CA1 neurons, forebrain ischemia induces the phosphorylation of the N-methyl-D-aspartate (NMDA) receptor 2A subunit at Ser1232 (phospho-Ser1232). Ser1232 phosphorylation is catalyzed by cyclin-dependent kinase 5 (Cdk5). Inhibiting endogenous Cdk5, or perturbing interactions between Cdk5 and NR2A subunits, abolished NR2A phosphorylation at Ser1232 and protected CA1 pyramidal neurons from ischemic insult. Thus, we conclude that modulation of NMDA receptors by Cdk5 is the primary intracellular event underlying the ischemic injury of CA1 pyramidal neurons.

UR - https://www.scopus.com/pages/publications/0141542665

M3 - Journal Article

SN - 1097-6256

VL - 6

SP - 1039

EP - 1047

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 10

ER -

Cdk5 activation induces hippocampal CA1 cell death by directly phosphorylating NMDA receptors

Abstract

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