Identification of amino acid residues that control functional behavior in GluR5 and GluR6 kainate receptors

Geoffrey T. Swanson; Robert W. Gereau IV; Tim Green; Stephen F. Heinemann

doi:10.1016/S0896-6273(00)80972-1

Identification of amino acid residues that control functional behavior in GluR5 and GluR6 kainate receptors

Geoffrey T. Swanson^*, Robert W. Gereau IV, Tim Green, Stephen F. Heinemann

^*Corresponding author for this work

Pharmacology

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

112 Scopus citations

Abstract

GluR5 and GluR6 kainate receptors differ in their responses to a variety of agonists, despite their relatively high primary sequence homology. We carried out a structure-function study to identify amino acids underlying these divergent responses. Patch clamp analysis of chimeric GluR5-GluR6 receptors indicated that several functionally dominant sites were localized to the C-terminal side of M1. All nonconserved amino acids in the region between M3 and M4 of GluR6 were then individually mutated to their GluR5 counterparts. We found that a single amino acid (N721 in GluR6) controls both AMPA sensitivity and domoate deactivation rates. Additionally, mutation of A689 in GluR6 slowed kainate desensitization. These functional effects were accompanied by alterations in binding affinities. These results support a critical role for these residues in receptor binding and gating activity.

Original language	English (US)
Pages (from-to)	913-926
Number of pages	14
Journal	Neuron
Volume	19
Issue number	4
DOIs	https://doi.org/10.1016/S0896-6273(00)80972-1
State	Published - Oct 1997

Funding

The authors would like to thank Peter Seeburg for the GluR5–2a cDNA. We also thank Connie Maron, Jane Sullivan, Bob Petroski, Cheryl Rogers, Carson Whiting, and Max Nanao for helpful advice and technical assistance. Melissa Hartley and the Core Sequencing Facility at the Salk Institute carried out the DNA sequencing. This work was supported by an NRSA fellowship (#1 F32 GM 18717-01) to G. T. S., an NRSA fellowship (#5 F32 NS 10079-02) to R. W. G., a National Institute for Neurological Diseases and Stroke grant (#2 RO1 NS 28709-06) to S. F. H., and a McKnight Endowment Fund for Neuroscience grant to S. F. H.

ASJC Scopus subject areas

General Neuroscience

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title = "Identification of amino acid residues that control functional behavior in GluR5 and GluR6 kainate receptors",

abstract = "GluR5 and GluR6 kainate receptors differ in their responses to a variety of agonists, despite their relatively high primary sequence homology. We carried out a structure-function study to identify amino acids underlying these divergent responses. Patch clamp analysis of chimeric GluR5-GluR6 receptors indicated that several functionally dominant sites were localized to the C-terminal side of M1. All nonconserved amino acids in the region between M3 and M4 of GluR6 were then individually mutated to their GluR5 counterparts. We found that a single amino acid (N721 in GluR6) controls both AMPA sensitivity and domoate deactivation rates. Additionally, mutation of A689 in GluR6 slowed kainate desensitization. These functional effects were accompanied by alterations in binding affinities. These results support a critical role for these residues in receptor binding and gating activity.",

author = "Swanson, {Geoffrey T.} and {Gereau IV}, {Robert W.} and Tim Green and Heinemann, {Stephen F.}",

note = "Funding Information: The authors would like to thank Peter Seeburg for the GluR5–2a cDNA. We also thank Connie Maron, Jane Sullivan, Bob Petroski, Cheryl Rogers, Carson Whiting, and Max Nanao for helpful advice and technical assistance. Melissa Hartley and the Core Sequencing Facility at the Salk Institute carried out the DNA sequencing. This work was supported by an NRSA fellowship (#1 F32 GM 18717-01) to G. T. S., an NRSA fellowship (#5 F32 NS 10079-02) to R. W. G., a National Institute for Neurological Diseases and Stroke grant (#2 RO1 NS 28709-06) to S. F. H., and a McKnight Endowment Fund for Neuroscience grant to S. F. H.",

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AU - Green, Tim

AU - Heinemann, Stephen F.

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PY - 1997/10

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Identification of amino acid residues that control functional behavior in GluR5 and GluR6 kainate receptors

Abstract

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