Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels.
Control of Slc7a5 sensitivity by the voltage-sensing domain of Kv1 channels.
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DOI：
10.7554/elife.54916
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发表时间：
2020-11-09
期刊：
影响因子：
7.7
通讯作者：
Kurata HT
中科院分区：
文献类型：
--
作者：
Lamothe SM;Sharmin N;Silver G;Satou M;Hao Y;Tateno T;Baronas VA;Kurata HT
许多电压依赖性离子通道由辅助蛋白调节。我们最近报道了氨基酸转运蛋白Slc 7a 5对Kv1.2钾通道的强大调节作用。在这项研究中，我们报告说，Kv1.1通道也受到Slc 7a 5的调节，尽管有不同的功能结果。在异源表达系统中，Kv1.1表现出显著的电流增强（“去抑制”），保持电位比-120 mV更负。敲低内源性Slc 7a 5导致更大的Kv1.1电流和强烈衰减的去抑制作用，这表明Slc 7a 5调节Kv1.1涉及通道抑制，可以通过超生理超极化电压逆转。我们研究了Kv1.1和Kv1.2的嵌合组合，证明电压敏感结构域的交换控制对Slc 7a 5的敏感性和响应，并在S1中定位特定位置，对Slc 7a 5敏感性具有显著影响。总的来说，我们的研究突出了多个Slc 7a 5敏感的Kv 1亚基，并确定了电压敏感域作为Slc 7a 5调节Kv 1通道的决定因素。
Many voltage-dependent ion channels are regulated by accessory proteins. We recently reported powerful regulation of Kv1.2 potassium channels by the amino acid transporter Slc7a5. In this study, we report that Kv1.1 channels are also regulated by Slc7a5, albeit with different functional outcomes. In heterologous expression systems, Kv1.1 exhibits prominent current enhancement ('disinhibition') with holding potentials more negative than −120 mV. Knockdown of endogenous Slc7a5 leads to larger Kv1.1 currents and strongly attenuates the disinhibition effect, suggesting that Slc7a5 regulation of Kv1.1 involves channel inhibition that can be reversed by supraphysiological hyperpolarizing voltages. We investigated chimeric combinations of Kv1.1 and Kv1.2, demonstrating that exchange of the voltage-sensing domain controls the sensitivity and response to Slc7a5, and localize a specific position in S1 with prominent effects on Slc7a5 sensitivity. Overall, our study highlights multiple Slc7a5-sensitive Kv1 subunits, and identifies the voltage-sensing domain as a determinant of Slc7a5 modulation of Kv1 channels.