Angiotensin receptor type 1 forms a complex with the transient outward potassium channel Kv4.3 and regulates its gating properties and intracellular localization
Angiotensin receptor type 1 forms a complex with the transient outward potassium channel Kv4.3 and regulates its gating properties and intracellular localization
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DOI：
10.1074/jbc.m405789200
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发表时间：
2004-11-12
影响因子：
4.8
通讯作者：
Cohen, IS
中科院分区：
文献类型：
--
作者：
Doronin, SV;Potapova, IA;Cohen, IS
我们报告了一种新的血管紧张素受体1型信号转导复合物。在这个复合体中，血管紧张素受体1型与钾通道α亚基Kv4.3结合并调节其细胞内分布和门控特性。Kv4.3与1型血管紧张素受体共定位，以及用绿色荧光蛋白的青色和黄绿色变体标记的两种蛋白之间的荧光共振能量传递表明，Kv4.3与1型血管紧张素受体在细胞内的位置非常接近。血管紧张素受体1型也与犬脑室的Kv4.3共免疫沉淀，或在人胚胎肾293细胞中与Kv4.3及其β亚基KChIP2共表达。用血管紧张素II处理细胞导致Kv4.3与血管紧张素受体1型复合物内在化。当受到血管紧张素II的刺激时，血管紧张素受体1通过将激活电压阈值移动到更正的值来调节细胞表面剩余Kv4.3通道的门控特性。我们假设血管紧张素受体1型为Kv4.3提供内化分子支架，并以这种方式调节离子通道的细胞表面表征。
We report a novel signal transduction complex of the angiotensin receptor type 1. In this complex the angiotensin receptor type 1 associates with the potassium channel alpha-subunit Kv4.3 and regulates its intracellular distribution and gating properties. Co-localization of Kv4.3 with angiotensin receptor type 1 and fluorescent resonance energy transfer between those two proteins labeled with cyan and yellow-green variants of green fluorescent protein revealed that Kv4.3 and angiotensin receptor type I are located in close proximity to each other in the cell. The angiotensin receptor type 1 also co-immunoprecipitates with Kv4.3 from canine ventricle or when co-expressed with Kv4.3 and its beta-subunit KChIP2 in human embryonic kidney 293 cells. Treatment of the cells with angiotensin II results in the internalization of Kv4.3 in a complex with the angiotensin receptor type 1. When stimulated with angiotensin II, angiotensin receptors type 1 modulate gating properties of the remaining Kv4.3 channels on the cell surface by shifting their activation voltage threshold to more positive values. We hypothesize that the angiotensin receptor type 1 provides its internalization molecular scaffold to Kv4.3 and in this way regulates the cell surface representation of the ion channel.