Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses

Marcia D. Antion; Louisa A. Christie; Allison M. Bond; Matthew B. Dalva; Anis Contractor

doi:10.1016/j.mcn.2010.07.011

Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses

Marcia D. Antion, Louisa A. Christie, Allison M. Bond, Matthew B. Dalva, Anis Contractor^*

^*Corresponding author for this work

Neuroscience

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

34 Scopus citations

Abstract

B-ephrin-EphB receptor signaling modulates NMDA receptors by inducing tyrosine phosphorylation of NR2 subunits. Ephrins and EphB RTKs are localized to postsynaptic compartments in the CA1, and therefore potentially interact in a non-canonical cis- configuration. However, it is not known whether cis- configured receptor-ligand signaling is utilized by this class of RTKs, and whether this might influence excitatory synapses. We found that ablation of ephrin-B3 results in an enhancement of the NMDA receptor component of synaptic transmission relative to the AMPA receptor component in CA1 synapses. Synaptic AMPA receptor expression is reduced in ephrin-B3 knockout mice, and there is a marked enhancement of tyrosine phosphorylation of the NR2B receptor subunit. In a reduced system co-expression of ephrin-B3 attenuated EphB2-mediated NR2B tyrosine phosphorylation. Moreover, phosphorylation of EphB2 was elevated in the hippocampus of ephrin-B3 knockout mice, suggesting that regulation of EphB2 activity is lost in these mice. Direct activation of EphB RTKs resulted in phosphorylation of NR2B and a potential signaling partner, the non-receptor tyrosine kinase Pyk2. Our data suggests that ephrin-B3 limits EphB RTK-mediated phosphorylation of the NR2B subunit through an inhibitory cis- interaction which is required for the correct function of glutamatergic CA1 synapses.

Original language	English (US)
Pages (from-to)	378-388
Number of pages	11
Journal	Molecular and Cellular Neuroscience
Volume	45
Issue number	4
DOIs	https://doi.org/10.1016/j.mcn.2010.07.011
State	Published - Dec 2010

Funding

We thank Mark Henkemeyer for generously providing ephrin-B3 mutant mice, Bryan Copits, Jian Xu, and Yongling Zhu for help with transfections, and Peter Penzes for providing cortical cultures. We also thank Peter Penzes for comments on the manuscript. This work was supported by a Mechanism of Aging and Dementia Training Program award ( NIA ) ( T32 AG020506 ) (to MDA) and grants from the National Institute of Health (NIDA, NIMH and NINDS) ( DA022727 and MH086425 to MBD, and NS049494 and NS058894 to AC).

Keywords

CA1
EphB2 RTK
Ephrin-B3
Excitatory synapse
Hippocampus
In cis signaling
NMDA receptor
Pyk2

ASJC Scopus subject areas

Cellular and Molecular Neuroscience
Molecular Biology
Cell Biology

Access to Document

10.1016/j.mcn.2010.07.011

Cite this

@article{777db09e4bc041b49f98c32ba475e222,

title = "Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses",

abstract = "B-ephrin-EphB receptor signaling modulates NMDA receptors by inducing tyrosine phosphorylation of NR2 subunits. Ephrins and EphB RTKs are localized to postsynaptic compartments in the CA1, and therefore potentially interact in a non-canonical cis- configuration. However, it is not known whether cis- configured receptor-ligand signaling is utilized by this class of RTKs, and whether this might influence excitatory synapses. We found that ablation of ephrin-B3 results in an enhancement of the NMDA receptor component of synaptic transmission relative to the AMPA receptor component in CA1 synapses. Synaptic AMPA receptor expression is reduced in ephrin-B3 knockout mice, and there is a marked enhancement of tyrosine phosphorylation of the NR2B receptor subunit. In a reduced system co-expression of ephrin-B3 attenuated EphB2-mediated NR2B tyrosine phosphorylation. Moreover, phosphorylation of EphB2 was elevated in the hippocampus of ephrin-B3 knockout mice, suggesting that regulation of EphB2 activity is lost in these mice. Direct activation of EphB RTKs resulted in phosphorylation of NR2B and a potential signaling partner, the non-receptor tyrosine kinase Pyk2. Our data suggests that ephrin-B3 limits EphB RTK-mediated phosphorylation of the NR2B subunit through an inhibitory cis- interaction which is required for the correct function of glutamatergic CA1 synapses.",

keywords = "CA1, EphB2 RTK, Ephrin-B3, Excitatory synapse, Hippocampus, In cis signaling, NMDA receptor, Pyk2",

author = "Antion, {Marcia D.} and Christie, {Louisa A.} and Bond, {Allison M.} and Dalva, {Matthew B.} and Anis Contractor",

note = "Funding Information: We thank Mark Henkemeyer for generously providing ephrin-B3 mutant mice, Bryan Copits, Jian Xu, and Yongling Zhu for help with transfections, and Peter Penzes for providing cortical cultures. We also thank Peter Penzes for comments on the manuscript. This work was supported by a Mechanism of Aging and Dementia Training Program award ( NIA ) ( T32 AG020506 ) (to MDA) and grants from the National Institute of Health (NIDA, NIMH and NINDS) ( DA022727 and MH086425 to MBD, and NS049494 and NS058894 to AC). Copyright: Copyright 2011 Elsevier B.V., All rights reserved.",

year = "2010",

month = dec,

doi = "10.1016/j.mcn.2010.07.011",

language = "English (US)",

volume = "45",

pages = "378--388",

journal = "Molecular and Cellular Neuroscience",

issn = "1044-7431",

publisher = "Academic Press Inc.",

number = "4",

}

TY - JOUR

T1 - Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses

AU - Antion, Marcia D.

AU - Christie, Louisa A.

AU - Bond, Allison M.

AU - Dalva, Matthew B.

AU - Contractor, Anis

N1 - Funding Information: We thank Mark Henkemeyer for generously providing ephrin-B3 mutant mice, Bryan Copits, Jian Xu, and Yongling Zhu for help with transfections, and Peter Penzes for providing cortical cultures. We also thank Peter Penzes for comments on the manuscript. This work was supported by a Mechanism of Aging and Dementia Training Program award ( NIA ) ( T32 AG020506 ) (to MDA) and grants from the National Institute of Health (NIDA, NIMH and NINDS) ( DA022727 and MH086425 to MBD, and NS049494 and NS058894 to AC). Copyright: Copyright 2011 Elsevier B.V., All rights reserved.

PY - 2010/12

Y1 - 2010/12

N2 - B-ephrin-EphB receptor signaling modulates NMDA receptors by inducing tyrosine phosphorylation of NR2 subunits. Ephrins and EphB RTKs are localized to postsynaptic compartments in the CA1, and therefore potentially interact in a non-canonical cis- configuration. However, it is not known whether cis- configured receptor-ligand signaling is utilized by this class of RTKs, and whether this might influence excitatory synapses. We found that ablation of ephrin-B3 results in an enhancement of the NMDA receptor component of synaptic transmission relative to the AMPA receptor component in CA1 synapses. Synaptic AMPA receptor expression is reduced in ephrin-B3 knockout mice, and there is a marked enhancement of tyrosine phosphorylation of the NR2B receptor subunit. In a reduced system co-expression of ephrin-B3 attenuated EphB2-mediated NR2B tyrosine phosphorylation. Moreover, phosphorylation of EphB2 was elevated in the hippocampus of ephrin-B3 knockout mice, suggesting that regulation of EphB2 activity is lost in these mice. Direct activation of EphB RTKs resulted in phosphorylation of NR2B and a potential signaling partner, the non-receptor tyrosine kinase Pyk2. Our data suggests that ephrin-B3 limits EphB RTK-mediated phosphorylation of the NR2B subunit through an inhibitory cis- interaction which is required for the correct function of glutamatergic CA1 synapses.

AB - B-ephrin-EphB receptor signaling modulates NMDA receptors by inducing tyrosine phosphorylation of NR2 subunits. Ephrins and EphB RTKs are localized to postsynaptic compartments in the CA1, and therefore potentially interact in a non-canonical cis- configuration. However, it is not known whether cis- configured receptor-ligand signaling is utilized by this class of RTKs, and whether this might influence excitatory synapses. We found that ablation of ephrin-B3 results in an enhancement of the NMDA receptor component of synaptic transmission relative to the AMPA receptor component in CA1 synapses. Synaptic AMPA receptor expression is reduced in ephrin-B3 knockout mice, and there is a marked enhancement of tyrosine phosphorylation of the NR2B receptor subunit. In a reduced system co-expression of ephrin-B3 attenuated EphB2-mediated NR2B tyrosine phosphorylation. Moreover, phosphorylation of EphB2 was elevated in the hippocampus of ephrin-B3 knockout mice, suggesting that regulation of EphB2 activity is lost in these mice. Direct activation of EphB RTKs resulted in phosphorylation of NR2B and a potential signaling partner, the non-receptor tyrosine kinase Pyk2. Our data suggests that ephrin-B3 limits EphB RTK-mediated phosphorylation of the NR2B subunit through an inhibitory cis- interaction which is required for the correct function of glutamatergic CA1 synapses.

KW - CA1

KW - EphB2 RTK

KW - Ephrin-B3

KW - Excitatory synapse

KW - Hippocampus

KW - In cis signaling

KW - NMDA receptor

KW - Pyk2

UR - http://www.scopus.com/inward/record.url?scp=77957970300&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957970300&partnerID=8YFLogxK

U2 - 10.1016/j.mcn.2010.07.011

DO - 10.1016/j.mcn.2010.07.011

M3 - Article

C2 - 20678574

AN - SCOPUS:77957970300

SN - 1044-7431

VL - 45

SP - 378

EP - 388

JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

IS - 4

ER -

Ephrin-B3 regulates glutamate receptor signaling at hippocampal synapses

Abstract

Funding

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this