Transmembrane topology of the glutamate receptor subunit GluR6

Katherine W. Roche, Lynn A. Raymond, Craig Blackstone, Richard L Huganir

Research output: Contribution to journalArticle

Abstract

Ionotropic glutamate receptors mediate most rapid excitatory synaptic transmission in the mammalian central nervous system. These receptors are divided into α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), kainate, and N-methyl-D-aspartate receptors based on pharmacological and electrophysiological characteristics. Ionotropic receptor subunits are integral membrane proteins that have been proposed to have a large extracellular ligand-binding N-terminal domain, four hydrophobic transmembrane domains, and an extracellular C-terminal domain. In this study we have shown that both AMPA receptor subunits (GluR1-4) and kainate receptor subunits (GluR6/7) are glycosylated in adult rat brain; however, the kainate receptor subunits are glycosylated to a greater extent. Examination of the sequences of AMPA and kainate receptors revealed that kainate receptors have several additional consensus sites for N-linked glycosylation; interestingly, one of these is located in the proposed major intracellular loop of the receptor subunits. To test the proposed transmembrane topology model for these receptors, we have used site-specific mutagenesis of the GluR6 subunit to remove the consensus glycosylation site located within the proposed intracellular loop. Mutagenesis of this site demonstrates that it is glycosylated in transiently transfected human embryonic kidney cells, which express functional kainate receptors. Since N-linked glycosylation has only been found to occur on extracellular domains of plasma membrane proteins, these results suggest that the proposed transmembrane topology model for the glutamate receptor subunits is incorrect. Combining these results with other recent data, we have proposed an alternative transmembrane topology model.

Original languageEnglish (US)
Pages (from-to)11679-11682
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number16
StatePublished - Apr 22 1994

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Kainic Acid Receptors
Glutamate Receptors
Glycosylation
Topology
Mutagenesis
Membrane Proteins
Isoxazoles
Ionotropic Glutamate Receptors
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
AMPA Receptors
Kainic Acid
Propionates
Site-Directed Mutagenesis
N-Methyl-D-Aspartate Receptors
Synaptic Transmission
Neurology
Blood Proteins
Cell membranes
Central Nervous System
Cell Membrane

ASJC Scopus subject areas

  • Biochemistry

Cite this

Roche, K. W., Raymond, L. A., Blackstone, C., & Huganir, R. L. (1994). Transmembrane topology of the glutamate receptor subunit GluR6. Journal of Biological Chemistry, 269(16), 11679-11682.

Transmembrane topology of the glutamate receptor subunit GluR6. / Roche, Katherine W.; Raymond, Lynn A.; Blackstone, Craig; Huganir, Richard L.

In: Journal of Biological Chemistry, Vol. 269, No. 16, 22.04.1994, p. 11679-11682.

Research output: Contribution to journalArticle

Roche, KW, Raymond, LA, Blackstone, C & Huganir, RL 1994, 'Transmembrane topology of the glutamate receptor subunit GluR6', Journal of Biological Chemistry, vol. 269, no. 16, pp. 11679-11682.
Roche KW, Raymond LA, Blackstone C, Huganir RL. Transmembrane topology of the glutamate receptor subunit GluR6. Journal of Biological Chemistry. 1994 Apr 22;269(16):11679-11682.
Roche, Katherine W. ; Raymond, Lynn A. ; Blackstone, Craig ; Huganir, Richard L. / Transmembrane topology of the glutamate receptor subunit GluR6. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 16. pp. 11679-11682.
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