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Stargazin modulates AMPA receptor gating and trafficking by distinct domains

被引：389
作者：
Tomita, S
Adesnik, H
Sekiguchi, M
Zhang, W
Wada, K
Howe, JR
Nicoll, RA
Bredt, DS
机构：
[1] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
[3] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA
[4] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Degenerat Neurol Dis, Tokyo 1878502, Japan
来源：
NATURE | 2005年 / 435卷 / 7045期
基金：
美国国家卫生研究院;
关键词：
D O I：
10.1038/nature03624
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
AMPA (alpha-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.
引用
收藏
页码：1052 / 1058
页数：7
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