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Stargazin modulates AMPA receptor gating and trafficking by distinct domains

Author

Listed:
  • Susumu Tomita

    (Department of Physiology)

  • Hillel Adesnik

    (University of California at San Francisco)

  • Masayuki Sekiguchi

    (National Center of Neurology and Psychiatry)

  • Wei Zhang

    (Yale University School of Medicine)

  • Keiji Wada

    (National Center of Neurology and Psychiatry)

  • James R. Howe

    (Yale University School of Medicine)

  • Roger A. Nicoll

    (Department of Physiology
    University of California at San Francisco)

  • David S. Bredt

    (Department of Physiology)

Abstract

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors mediate fast excitatory synaptic transmission in the brain. These ion channels rapidly deactivate and desensitize, which determine the time course of synaptic transmission. Here, we find that the AMPA receptor interacting protein, stargazin, not only mediates AMPA receptor trafficking but also shapes synaptic responses by slowing channel deactivation and desensitization. The cytoplasmic tail of stargazin determines receptor trafficking, whereas the ectodomain controls channel properties. Stargazin alters AMPA receptor kinetics by increasing the rate of channel opening. Disrupting the interaction of stargazin ectodomain with hippocampal AMPA receptors alters the amplitude and shape of synaptic responses, establishing a crucial function for stargazin in controlling the efficacy of synaptic transmission in the brain.

Suggested Citation

  • Susumu Tomita & Hillel Adesnik & Masayuki Sekiguchi & Wei Zhang & Keiji Wada & James R. Howe & Roger A. Nicoll & David S. Bredt, 2005. "Stargazin modulates AMPA receptor gating and trafficking by distinct domains," Nature, Nature, vol. 435(7045), pages 1052-1058, June.
    • Handle: RePEc:nat:nature:v:435:y:2005:i:7045:d:10.1038_nature03624
    DOI: 10.1038/nature03624
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    Cited by:

    1. 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.
    2. Beatriz Herguedas & Bianka K. Kohegyi & Jan-Niklas Dohrke & Jake F. Watson & Danyang Zhang & Hinze Ho & Saher A. Shaikh & Remigijus Lape & James M. Krieger & Ingo H. Greger, 2022. "Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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