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Research ArticleMINIREVIEWS

Control of Assembly and Function of Glutamate Receptors by the Amino-Terminal Domain

Kasper B. Hansen, Hiro Furukawa and Stephen F. Traynelis
Molecular Pharmacology October 2010, 78 (4) 535-549; DOI: https://doi.org/10.1124/mol.110.067157
Kasper B. Hansen
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Hiro Furukawa
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Stephen F. Traynelis
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Abstract

The extracellular amino-terminal domains (ATDs) of the ionotropic glutamate receptor subunits form a semiautonomous component of all glutamate receptors that resides distal to the membrane and controls a surprisingly diverse set of receptor functions. These functions include subunit assembly, receptor trafficking, channel gating, agonist potency, and allosteric modulation. The many divergent features of the different ionotropic glutamate receptor classes and different subunits within a class may stem from differential regulation by the amino-terminal domains. The emerging knowledge of the structure and function of the amino-terminal domains reviewed here may enable targeting of this region for the therapeutic modulation of glutamatergic signaling. Toward this end, NMDA receptor antagonists that interact with the GluN2B ATD show promise in animal models of ischemia, neuropathic pain, and Parkinson's disease.

Footnotes

  • S.F.T. holds an equity position in NeurOp Inc.

  • This work was supported by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grants NS036654, NS065371]; National Institutes of Health National Institute of Mental Health [Grant MH085926-01A1]; the Alzheimer's Association; the Lundbeck Foundation; and the Villum Kann Rasmussen Foundation.

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.110.067157.

  • ABBREVIATIONS:

    AMPA
    α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate
    NMDA
    N-methyl-d-aspartate
    mGluR
    metabotropic glutamate receptor
    ATD
    amino-terminal domain
    CP-101,606
    traxoprodil mesylate
    PDB
    Protein Data Bank.

  • Received June 27, 2010.
  • Accepted July 21, 2010.
  • Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 78 (4)
Molecular Pharmacology
Vol. 78, Issue 4
1 Oct 2010
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Research ArticleMINIREVIEWS

Control of Assembly and Function of Glutamate Receptors by the Amino-Terminal Domain

Kasper B. Hansen, Hiro Furukawa and Stephen F. Traynelis
Molecular Pharmacology October 1, 2010, 78 (4) 535-549; DOI: https://doi.org/10.1124/mol.110.067157

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Research ArticleMINIREVIEWS

Control of Assembly and Function of Glutamate Receptors by the Amino-Terminal Domain

Kasper B. Hansen, Hiro Furukawa and Stephen F. Traynelis
Molecular Pharmacology October 1, 2010, 78 (4) 535-549; DOI: https://doi.org/10.1124/mol.110.067157
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