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Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms

Author

Listed:
  • Lu Chen

    (Cellular and Molecular Pharmacology,)

  • Dane M. Chetkovich

    (Departments of Physiology
    University of California)

  • Ronald S. Petralia

    (Laboratory of Neurochemistry, NIDCD, National Institutes of Health)

  • Neal T. Sweeney

    (Departments of Physiology)

  • Yoshimi Kawasaki

    (Departments of Physiology)

  • Robert J. Wenthold

    (Laboratory of Neurochemistry, NIDCD, National Institutes of Health)

  • David S. Bredt

    (Departments of Physiology)

  • Roger A. Nicoll

    (Cellular and Molecular Pharmacology,
    Departments of Physiology)

Abstract

Stargazer, an ataxic and epileptic mutant mouse, lacks functional AMPA (α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate) receptors on cerebellar granule cells. Stargazin, the mutated protein, interacts with both AMPA receptor subunits and synaptic PDZ proteins, such as PSD-95. The interaction of stargazin with AMPA receptor subunits is essential for delivering functional receptors to the surface membrane of granule cells, whereas its binding with PSD-95 and related PDZ proteins through a carboxy-terminal PDZ-binding domain is required for targeting the AMPA receptor to synapses. Expression of a mutant stargazin lacking the PDZ-binding domain in hippocampal pyramidal cells disrupts synaptic AMPA receptors, indicating that stargazin-like mechanisms for targeting AMPA receptors may be widespread in the central nervous system.

Suggested Citation

  • Lu Chen & Dane M. Chetkovich & Ronald S. Petralia & Neal T. Sweeney & Yoshimi Kawasaki & Robert J. Wenthold & David S. Bredt & Roger A. Nicoll, 2000. "Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms," Nature, Nature, vol. 408(6815), pages 936-943, December.
    • Handle: RePEc:nat:nature:v:408:y:2000:i:6815:d:10.1038_35050030
    DOI: 10.1038/35050030
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    Cited by:

    1. Caleigh M Azumaya & Emily L Days & Paige N Vinson & Shaun Stauffer & Gary Sulikowski & C David Weaver & Terunaga Nakagawa, 2017. "Screening for AMPA receptor auxiliary subunit specific modulators," PLOS ONE, Public Library of Science, vol. 12(3), pages 1-23, March.
    2. Hang Zhou & Guo-Qiang Bi & Guosong Liu, 2024. "Intracellular magnesium optimizes transmission efficiency and plasticity of hippocampal synapses by reconfiguring their connectivity," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    3. Diogo Bessa-Neto & Gerti Beliu & Alexander Kuhlemann & Valeria Pecoraro & Sören Doose & Natacha Retailleau & Nicolas Chevrier & David Perrais & Markus Sauer & Daniel Choquet, 2021. "Bioorthogonal labeling of transmembrane proteins with non-canonical amino acids unveils masked epitopes in live neurons," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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