The desensitization gate of inhibitory Cys-loop receptors.
The desensitization gate of inhibitory Cys-loop receptors.
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DOI：
10.1038/ncomms7829
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发表时间：
2015-04-20
影响因子：
16.6
通讯作者：
Smart, Trevor G.
中科院分区：
文献类型：
--
作者：
Gielen, Marc;Thomas, Philip;Smart, Trevor G.
cys环神经递质门控离子通道对整个神经系统的通信至关重要。激活后，这些受体进入一种脱敏状态，在这种状态下，即使神经递质分子仍然结合，离子通道也会关闭。迄今为止，Cys-loop受体这一最基本特性的分子决定因素仍然难以捉摸。在这里，我们提出了Cys-loop GABAA （GABAARs）和甘氨酸受体（GlyRs）脱敏的一般机制，这两种受体都介导快速抑制性突触传递。脱敏是由第二和第三跨膜段之间的相互作用调节的，它们影响细胞内末端附近的离子通道管腔。GABAAR和GlyR孔阻滞剂微毒素阻止脱敏，与其深通道结合位点重叠的物理脱敏门一致。激活后，cys环神经递质门控离子通道逐渐脱敏，电导关闭。在这里，Gielen等人提出了一种脱敏机制，其中跨膜域之间的界面被重塑以收缩细胞内端的通道孔。
Cys-loop neurotransmitter-gated ion channels are vital for communication throughout the nervous system. Following activation, these receptors enter into a desensitized state in which the ion channel shuts even though the neurotransmitter molecules remain bound. To date, the molecular determinants underlying this most fundamental property of Cys-loop receptors have remained elusive. Here we present a generic mechanism for the desensitization of Cys-loop GABAA (GABAARs) and glycine receptors (GlyRs), which both mediate fast inhibitory synaptic transmission. Desensitization is regulated by interactions between the second and third transmembrane segments, which affect the ion channel lumen near its intracellular end. The GABAAR and GlyR pore blocker picrotoxin prevented desensitization, consistent with its deep channel-binding site overlapping a physical desensitization gate. Following activation, Cys-loop neurotransmitter-gated ion channels gradually desensitize and conductance shuts down. Here Gielen et al. present a mechanism for desensitization in which the interface between transmembrane domains is remodelled to constrict the channel pore at the intracellular end.
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影响因子：
--
作者：
Breitinger, HG;Lanig, H;Becker, CM
通讯作者：
Becker, CM
影响因子：
64.8
作者：
Hilf, Ricarda J. C.;Dutzler, Raimund
通讯作者：
Dutzler, Raimund
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1085/jgp.200609639
发表时间：
2007-02
期刊：
The Journal of general physiology
影响因子：
--
作者：
Bali M;Akabas MH
通讯作者：
Akabas MH
影响因子：
56.9
作者：
Heine, Martin;Groc, Laurent;Choquet, Daniel
通讯作者：
Choquet, Daniel