Potassium channels act as chemosensors for solute transporters.
Potassium channels act as chemosensors for solute transporters.
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钾通道充当溶质转运蛋白的化学传感器。
DOI：
10.1038/s42003-020-0820-9
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发表时间：
2020
影响因子：
5.9
通讯作者：
Abbott,GeoffreyW
中科院分区：
文献类型：
--
作者：
Manville,RίanW;Abbott,GeoffreyW
钾通道在体内与溶质转运蛋白形成物理复合物，但对其可能的信号传导方式和潜在机制的范围知之甚少。产生神经元M-电流的KCNQ 2/3钾通道是电压门控的，其活性也受到各种小分子结合的刺激。KCNQ 2/3在哺乳动物神经元中与钠偶联肌肌醇转运体（SMITs）形成钙调复合物。在此，我们报道了神经递质γ-氨基丁酸（GABA）和其他小分子物质直接调节大鼠背根神经节中的肌醇转运，并通过体外人SMIT 1-KCNQ 2/3复合物，诱导不同的KCNQ 2/3孔构象。反过来，SMIT 1调节GABA和相关代谢物的KCNQ 2/3传感。离子渗透和诱变研究表明，SMIT 1和GABA类似地改变KCNQ 2/3孔构象，但通过不同的KCNQ亚基和分子机制。因此，KCNQ通道作为化学传感器，使共代谢的肌肌醇转运蛋白，以响应不同的刺激，包括神经递质，代谢产物和药物。
Potassium channels form physical complexes with solute transporters in vivo, yet little is known about their range of possible signaling modalities and the underlying mechanisms. The KCNQ2/3 potassium channel, which generates neuronal M-current, is voltage-gated and its activity is also stimulated by binding of various small molecules. KCNQ2/3 forms reciprocally regulating complexes with sodium-coupledmyo-inositol transporters (SMITs) in mammalian neurons. Here, we report that the neurotransmitter γ-aminobutyric acid (GABA) and other small molecules directly regulatemyo-inositol transport in rat dorsal root ganglia, and by human SMIT1-KCNQ2/3 complexes in vitro, by inducing a distinct KCNQ2/3 pore conformation. Reciprocally, SMIT1 tunes KCNQ2/3 sensing of GABA and related metabolites. Ion permeation and mutagenesis studies suggest that SMIT1 and GABA similarly alter KCNQ2/3 pore conformation but via different KCNQ subunits and molecular mechanisms. KCNQ channels therefore act as chemosensors to enable co-assembledmyo-inositol transporters to respond to diverse stimuli including neurotransmitters, metabolites and drugs.