Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

Christoph Straub; Yoav Noam; Toshihiro Nomura; Miwako Yamasaki; Dan Yan; Herman B. Fernandes; Ping Zhang; James R. Howe; Masahiko Watanabe; Anis Contractor; Susumu Tomita

doi:10.1016/j.celrep.2016.05.093

Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

Christoph Straub, Yoav Noam, Toshihiro Nomura, Miwako Yamasaki, Dan Yan, Herman B. Fernandes, Ping Zhang, James R. Howe, Masahiko Watanabe, Anis Contractor, Susumu Tomita^*

^*Corresponding author for this work

Neuroscience

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

29 Scopus citations

Abstract

Synaptic communication between neurons requires the precise localization of neurotransmitter receptors to the correct synapse type. Kainate-type glutamate receptors restrict synaptic localization that is determined by the afferent presynaptic connection. The mechanisms that govern this input-specific synaptic localization remain unclear. Here, we examine how subunit composition and specific subunit domains contribute to synaptic localization of kainate receptors. The cytoplasmic domain of the GluK2 low-affinity subunit stabilizes kainate receptors at synapses. In contrast, the extracellular domain of the GluK4/5 high-affinity subunit synergistically controls the synaptic specificity of kainate receptors through interaction with C1q-like proteins. Thus, the input-specific synaptic localization of the native kainate receptor complex involves two mechanisms that underlie specificity and stabilization of the receptor at synapses.

Original language	English (US)
Pages (from-to)	531-544
Number of pages	14
Journal	Cell reports
Volume	16
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2016.05.093
State	Published - Jul 12 2016

Funding

The authors thank the members of S.T.’s and A.C.’s labs for helpful discussions. We thank Dr. Megumi Morimoto-Tomita for generating various reagents, Dr. S.F. Heinemann (Salk Institute), Dr. Peter Seeburg (Max Planck Institute), Deltagen, Genentech, KOMP for generating each of GluK2/4/5 knockouts, GluA1 knockout, Neto2 knockout, Neto1 knockout mice, and the Jackson laboratory and MMRRC for maintaining GluK2, GluK5, Neto2 knockout, and stargazer mice. Parts of this study were supported by NIH/NIMH R01 MH085080 and the Yale fund (S.T.) and NIH/NIMH R01 MH099114 (A.C.). M.W. is supported by Grants-in-Aid for Scientific Research provided by the Ministry of Education, Culture, Sports, Science and Technology of Japan. C.S. was supported by a Boehringer-Ingelheim Fonds PhD fellowship, and Y.N was supported by NIH/NINDS NRSA post-doctoral fellowship (F32 NS093952).

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2016.05.093

Cite this

@article{b51a52a29c2c4618af01cbdb3ef5e099,

title = "Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor",

abstract = "Synaptic communication between neurons requires the precise localization of neurotransmitter receptors to the correct synapse type. Kainate-type glutamate receptors restrict synaptic localization that is determined by the afferent presynaptic connection. The mechanisms that govern this input-specific synaptic localization remain unclear. Here, we examine how subunit composition and specific subunit domains contribute to synaptic localization of kainate receptors. The cytoplasmic domain of the GluK2 low-affinity subunit stabilizes kainate receptors at synapses. In contrast, the extracellular domain of the GluK4/5 high-affinity subunit synergistically controls the synaptic specificity of kainate receptors through interaction with C1q-like proteins. Thus, the input-specific synaptic localization of the native kainate receptor complex involves two mechanisms that underlie specificity and stabilization of the receptor at synapses.",

author = "Christoph Straub and Yoav Noam and Toshihiro Nomura and Miwako Yamasaki and Dan Yan and Fernandes, {Herman B.} and Ping Zhang and Howe, {James R.} and Masahiko Watanabe and Anis Contractor and Susumu Tomita",

note = "Publisher Copyright: {\textcopyright} 2016",

year = "2016",

month = jul,

day = "12",

doi = "10.1016/j.celrep.2016.05.093",

language = "English (US)",

volume = "16",

pages = "531--544",

journal = "Cell reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

AU - Straub, Christoph

AU - Noam, Yoav

AU - Nomura, Toshihiro

AU - Yamasaki, Miwako

AU - Yan, Dan

AU - Fernandes, Herman B.

AU - Zhang, Ping

AU - Howe, James R.

AU - Watanabe, Masahiko

AU - Contractor, Anis

AU - Tomita, Susumu

PY - 2016/7/12

Y1 - 2016/7/12

N2 - Synaptic communication between neurons requires the precise localization of neurotransmitter receptors to the correct synapse type. Kainate-type glutamate receptors restrict synaptic localization that is determined by the afferent presynaptic connection. The mechanisms that govern this input-specific synaptic localization remain unclear. Here, we examine how subunit composition and specific subunit domains contribute to synaptic localization of kainate receptors. The cytoplasmic domain of the GluK2 low-affinity subunit stabilizes kainate receptors at synapses. In contrast, the extracellular domain of the GluK4/5 high-affinity subunit synergistically controls the synaptic specificity of kainate receptors through interaction with C1q-like proteins. Thus, the input-specific synaptic localization of the native kainate receptor complex involves two mechanisms that underlie specificity and stabilization of the receptor at synapses.

AB - Synaptic communication between neurons requires the precise localization of neurotransmitter receptors to the correct synapse type. Kainate-type glutamate receptors restrict synaptic localization that is determined by the afferent presynaptic connection. The mechanisms that govern this input-specific synaptic localization remain unclear. Here, we examine how subunit composition and specific subunit domains contribute to synaptic localization of kainate receptors. The cytoplasmic domain of the GluK2 low-affinity subunit stabilizes kainate receptors at synapses. In contrast, the extracellular domain of the GluK4/5 high-affinity subunit synergistically controls the synaptic specificity of kainate receptors through interaction with C1q-like proteins. Thus, the input-specific synaptic localization of the native kainate receptor complex involves two mechanisms that underlie specificity and stabilization of the receptor at synapses.

UR - http://www.scopus.com/inward/record.url?scp=84992507367&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992507367&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.05.093

DO - 10.1016/j.celrep.2016.05.093

M3 - Article

C2 - 27346345

AN - SCOPUS:84992507367

SN - 2211-1247

VL - 16

SP - 531

EP - 544

JO - Cell reports

JF - Cell reports

IS - 2

ER -

Distinct Subunit Domains Govern Synaptic Stability and Specificity of the Kainate Receptor

Abstract

Funding

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this