Stargazin modulates AMPA receptor gating and trafficking by distinct domains

Susumu Tomita, Hillel Adesnik, Masayuki Sekiguchi, Wei Zhang, Keiji Wada, James R. Howe, Roger A. Nicoll () and David S. Bredt ()
Additional contact information
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
David S. Bredt: Department of Physiology

Nature, 2005, vol. 435, issue 7045, 1052-1058

Abstract: 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.

Date: 2005
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DOI: 10.1038/nature03624

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