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Autoantibodies Against an Extracellular Peptide of the GluR3 Subtype of AMPA Receptors Activate Both Homomeric and Heteromeric AMPA Receptor Channels

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Abstract

Autoantibodies to the GluR3-subtype of AMPA/glutamate receptors are found in the sera and cerebrospinal fluid of some individuals with epilepsy. They could possibly play a role in the pathophysiology of epilepsy since anti-GluR3 sera display glutamatergic agonist activity. We have investigated here the ability of affinity-purified antibodies (Abs) directed against the immunogenic peptide GluR3B (amino-acid 372–395) to interact with and activate recombinant GluR3-receptor channels expressed by Xenopus oocytes. We report here that the affinity-purified anti-GluR3B Abs directly activate GluR3-containing homomeric and heteromeric AMPA receptor complexes without the requirement of neuronal, glial or blood ancillary molecules. We present some of the properties of the purified anti-GluR3B Abs and discuss the possible physiological or pathological consequences of their activation of glutamate receptors.

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Article 01 August 2014

Abbreviations

a.a:

amino acid

Ab:

antibody

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid

BSA:

bovine serum albumin

CFA:

complete Freund’s adjuvant

CNQX:

6-cyano-7-nitroquinoxaline-2,3-dione

DNQX:

6,7-dinitroquinoxaline-2,3-dione

ELISA:

enzyme-linked immunosorbent assay

GluR:

glutamate receptor

IgG:

immunoglobulin

KA:

kainate

LAOBP:

lysine–arginine–ornithine binding protein

LIVBP:

leucine–isoleucine–valine binding protein

NMDA:

N-methyl-d-aspartate

NTD:

N-terminus domain

PBS:

phosphate buffered saline

RE:

Rasmussen’s Encephalitis

RT:

room temperature

S1–S2:

the two lobes of LAOBP domain which form the ligand-binding core

SD:

standard deviation

SEM:

standard error of the mean

CSF:

cerebrospinal fluid

GluR3:

GluR3 subtype of AMPA/glutamate ion channel receptors

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Acknowledgments

This work was supported in part by grants from the Anne Kinston Estate, the Nella and Leon Benoziyo Center for Neurological Diseases, the Irwin Green Fund for Studying the Development of the Brain and the Carl and Micaela Einhorn-Dominic Institute for Brain Research. KCKM is indebted to Joseline Ratnam for introducing her to the electrophysiological methods of study of Xenopus oocytes, and for support and friendship. VIT is the incumbent of the Louis and Florence Katz-Cohen Chair of Neuropharmacology.

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Authors and Affiliations

  1. Department of Neurobiology, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Katayun Cohen-Kashi Malina, Yonatan Ganor, Mia Levite & Vivian I. Teichberg

Authors
  1. Katayun Cohen-Kashi Malina
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  2. Yonatan Ganor
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  3. Mia Levite
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  4. Vivian I. Teichberg
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Correspondence to Vivian I. Teichberg.

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Cohen-Kashi Malina, K., Ganor, Y., Levite, M. et al. Autoantibodies Against an Extracellular Peptide of the GluR3 Subtype of AMPA Receptors Activate Both Homomeric and Heteromeric AMPA Receptor Channels. Neurochem Res 31, 1181–1190 (2006). https://doi.org/10.1007/s11064-006-9143-6

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  • DOI: https://doi.org/10.1007/s11064-006-9143-6

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