The down-regulation of tyrosine phosphatase SHP2 activity is involved in the removal of surface AMPA receptors in long term depression

Hongxu Zhou; Yacong Xie; Weiqing Fang; Yonglan Du; Jinqi Zhou; Lijun Du; Bin Zhang

doi:10.1016/j.neulet.2022.136636

The down-regulation of tyrosine phosphatase SHP2 activity is involved in the removal of surface AMPA receptors in long term depression

Hongxu Zhou, Yacong Xie, Weiqing Fang, Yonglan Du, Jinqi Zhou, Lijun Du, Bin Zhang

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

3 Scopus citations

Abstract

Hebbian-type synaptic plasticity which includes long term potentiation (LTP) and long term depression (LTD), is the main cellular mechanism underlying learning and memory. Effective activity and synaptic content of tyrosine phosphatase SHP2 are required for AMPA receptor trafficking during LTP. However, the role of SHP2 in LTD has not been fully elucidated. This study shows that the phosphorylation level of SHP2 at Y542 decreased after LTD induction either in hippocampal cultures or acute CA1 mini slices. This change occurred at least 10 min after LTD induction and was alleviated by administration of NMDA receptor antagonist, APV. Furthermore, the SHP2 mutant (D61G), found in Noonan syndrome patients, prevented the removal of surface AMPA receptors during chemical-induced LTD on cultured hippocampal neurons. The results revealed a molecular basis of regulatory role of SHP2 in long term depression, thus expands our understanding of the SHP2 function in learning and memory.

Original language	English
Article number	136636
Journal	Neuroscience Letters
Volume	779
DOIs	https://doi.org/10.1016/j.neulet.2022.136636
State	Published - 14 May 2022
Externally published	Yes

Keywords

AMPA receptor
D61G
LTD
SHP2
Synaptic plasticity
Y542

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10.1016/j.neulet.2022.136636

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title = "The down-regulation of tyrosine phosphatase SHP2 activity is involved in the removal of surface AMPA receptors in long term depression",

abstract = "Hebbian-type synaptic plasticity which includes long term potentiation (LTP) and long term depression (LTD), is the main cellular mechanism underlying learning and memory. Effective activity and synaptic content of tyrosine phosphatase SHP2 are required for AMPA receptor trafficking during LTP. However, the role of SHP2 in LTD has not been fully elucidated. This study shows that the phosphorylation level of SHP2 at Y542 decreased after LTD induction either in hippocampal cultures or acute CA1 mini slices. This change occurred at least 10 min after LTD induction and was alleviated by administration of NMDA receptor antagonist, APV. Furthermore, the SHP2 mutant (D61G), found in Noonan syndrome patients, prevented the removal of surface AMPA receptors during chemical-induced LTD on cultured hippocampal neurons. The results revealed a molecular basis of regulatory role of SHP2 in long term depression, thus expands our understanding of the SHP2 function in learning and memory.",

keywords = "AMPA receptor, D61G, LTD, SHP2, Synaptic plasticity, Y542",

author = "Hongxu Zhou and Yacong Xie and Weiqing Fang and Yonglan Du and Jinqi Zhou and Lijun Du and Bin Zhang",

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doi = "10.1016/j.neulet.2022.136636",

language = "English",

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T1 - The down-regulation of tyrosine phosphatase SHP2 activity is involved in the removal of surface AMPA receptors in long term depression

AU - Zhou, Hongxu

AU - Xie, Yacong

AU - Fang, Weiqing

AU - Du, Yonglan

AU - Zhou, Jinqi

AU - Du, Lijun

AU - Zhang, Bin

PY - 2022/5/14

Y1 - 2022/5/14

N2 - Hebbian-type synaptic plasticity which includes long term potentiation (LTP) and long term depression (LTD), is the main cellular mechanism underlying learning and memory. Effective activity and synaptic content of tyrosine phosphatase SHP2 are required for AMPA receptor trafficking during LTP. However, the role of SHP2 in LTD has not been fully elucidated. This study shows that the phosphorylation level of SHP2 at Y542 decreased after LTD induction either in hippocampal cultures or acute CA1 mini slices. This change occurred at least 10 min after LTD induction and was alleviated by administration of NMDA receptor antagonist, APV. Furthermore, the SHP2 mutant (D61G), found in Noonan syndrome patients, prevented the removal of surface AMPA receptors during chemical-induced LTD on cultured hippocampal neurons. The results revealed a molecular basis of regulatory role of SHP2 in long term depression, thus expands our understanding of the SHP2 function in learning and memory.

AB - Hebbian-type synaptic plasticity which includes long term potentiation (LTP) and long term depression (LTD), is the main cellular mechanism underlying learning and memory. Effective activity and synaptic content of tyrosine phosphatase SHP2 are required for AMPA receptor trafficking during LTP. However, the role of SHP2 in LTD has not been fully elucidated. This study shows that the phosphorylation level of SHP2 at Y542 decreased after LTD induction either in hippocampal cultures or acute CA1 mini slices. This change occurred at least 10 min after LTD induction and was alleviated by administration of NMDA receptor antagonist, APV. Furthermore, the SHP2 mutant (D61G), found in Noonan syndrome patients, prevented the removal of surface AMPA receptors during chemical-induced LTD on cultured hippocampal neurons. The results revealed a molecular basis of regulatory role of SHP2 in long term depression, thus expands our understanding of the SHP2 function in learning and memory.

KW - AMPA receptor

KW - D61G

KW - LTD

KW - SHP2

KW - Synaptic plasticity

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DO - 10.1016/j.neulet.2022.136636

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VL - 779

JO - Neuroscience Letters

JF - Neuroscience Letters

M1 - 136636

ER -

The down-regulation of tyrosine phosphatase SHP2 activity is involved in the removal of surface AMPA receptors in long term depression

Abstract

Keywords

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