Phosphoinositides modulate the voltage dependence of two-pore channel 3
Phosphoinositides modulate the voltage dependence of two-pore channel 3
复制标题
磷酸肌醇调节双孔通道 3 的电压依赖性
DOI：
10.1085/jgp.201812285
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发表时间：
2019
期刊：
影响因子：
3.8
通讯作者：
Kubo Y
中科院分区：
文献类型：
--
作者：
Shimomura T;Kubo Y
双孔通道或双孔Na+通道（TPC）含有两个同源结构域，每个结构域含有典型的电压依赖性阳离子通道的功能单元。每个结构域被认为负责磷酸肌醇（PI）结合或电压感应。在TPC家族的三个成员中，TPC 1和TPC 2被PI（3，5）P2激活，而TPC 3被认为不受任何PI的影响。在这里，我们报告说，TPC 3是敏感的PI（3，4）P2和PI（3，5）P2，但不PI（4，5）P2，并在非洲爪蟾卵母细胞的去极化诱导TPC 3电流的极缓慢增加是由于生产PI（3，4）P2。类似于TPC 1，结构域I中的碱性氨基酸残基簇对于PI敏感性是关键的，但具有可允许TPC 3对PI（3，4）P2和PI（3，5）P2两者敏感的轻微变化。我们还发现，TPC 3具有独特的PI依赖的电压依赖性调制机制，这是通过结构域I和结构域II之间的特定桥接相互作用实现的。总之，这些发现表明TPC 3是TPC家族的独特成员，其感测PI并显示PI结合和电压依赖性门控之间的强耦合。
Two-pore channels, or two-pore Na+ channels (TPCs), contain two homologous domains, each containing a functional unit typical of voltage-dependent cation channels. Each domain is considered to be responsible for either phosphoinositide (PI) binding or voltage sensing. Among the three members of the TPC family, TPC1 and TPC2 are activated by PI (3, 5) P2, while TPC3 has been thought not to be affected by any PIs. Here, we report that TPC3 is sensitive to PI (3, 4) P2 and PI (3, 5) P2, but not to PI (4, 5) P2, and that the extremely slow increase in TPC3 currents induced by depolarization in Xenopus oocytes is due to the production of PI (3, 4) P2. Similarly to TPC1, the cluster of basic amino acid residues in domain I is critical for PI sensitivity, but with a slight variation that may allow TPC3 to be sensitive to both PI (3, 4) P2 and PI (3, 5) P2. We also found that TPC3 has a unique PI-dependent modulation mechanism of voltage dependence, which is achieved by a specific bridging interaction between domain I and domain II. Taken together, these findings show that TPC3 is a unique member of the TPC family that senses PIs and displays a strong coupling between PI binding and voltage-dependent gating.
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影响因子：
18.2
作者：
Xu H;Ren D
通讯作者：
Ren D
影响因子：
16.6
作者：
Dong, Xian-ping;Shen, Dongbiao;Wang, Xiang;Dawson, Taylor;Li, Xinran;Zhang, Qi;Cheng, Xiping;Zhang, Yanling;Weisman, Lois S.;Delling, Markus;Xu, Haoxing
通讯作者：
Xu, Haoxing
DOI：
10.1073/pnas.79.10.3188
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BAUD, C;KADO, RT;MARCHER, K
通讯作者：
MARCHER, K
影响因子：
64.8
作者：
Posor, York;Eichhorn-Gruenig, Marielle;Haucke, Volker
通讯作者：
Haucke, Volker
DOI：
10.1007/bf00591094
发表时间：
1985
期刊：
Pflügers Archiv
影响因子：
--
作者：
A. Peres;E. Mancinelli
通讯作者：
E. Mancinelli