1. Department of Physiology,
2. Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, California 94143, USA
3. Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
4. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan
5. These authors contributed equally to this work

Correspondence to: Roger A. Nicoll^1,2David S. Bredt¹ Correspondence and requests for materials should be addressed to D.S.B. (Email: bredt@itsa.ucsf.edu) or R.A.N. (Email: nicoll@cmp.ucsf.edu).

Abstract

AMPA (-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.

1. Department of Physiology,
2. Department of Cellular and Molecular Pharmacology, University of California at San Francisco, San Francisco, California 94143, USA
3. Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
4. Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan
5. These authors contributed equally to this work

Correspondence to: Roger A. Nicoll^1,2David S. Bredt¹ Correspondence and requests for materials should be addressed to D.S.B. (Email: bredt@itsa.ucsf.edu) or R.A.N. (Email: nicoll@cmp.ucsf.edu).

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