Reciprocal interaction with G-actin and tropomyosin is essential for aquaporin-2 trafficking.
Reciprocal interaction with G-actin and tropomyosin is essential for aquaporin-2 trafficking.
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DOI：
10.1083/jcb.200709177
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发表时间：
2008-08-11
期刊：
影响因子：
--
通讯作者：
Sasaki S
中科院分区：
文献类型：
--
作者：
Noda Y;Horikawa S;Kanda E;Yamashita M;Meng H;Eto K;Li Y;Kuwahara M;Hirai K;Pack C;Kinjo M;Okabe S;Sasaki S
水通道水通道蛋白-2(AQP2)转运到顶膜及其在肾脏集合管的加压素和蛋白激酶A(PKA)依赖的调节是维持机体水平衡的关键。我们以前发现了一个AQP2结合蛋白复合体，包括肌动蛋白和原肌球蛋白-5b(TM5b)。我们发现，AQP2和肌动蛋白细胞骨架之间的动态相互作用是启动AQP2根尖靶向的关键。重组脂质体中AQP2与G-肌动蛋白的特异性结合受PKA磷酸化的负调控。双色荧光互相关光谱在单分子分辨率下显示活上皮细胞中AQP2与G-肌动蛋白的局部相互作用。环磷酸腺苷信号和AQP2磷酸化从G-肌动蛋白释放AQP2。反过来，AQP2的磷酸化增加了它与TM5b的亲和力，导致TM5b与F-肌动蛋白结合的减少，从而导致F-肌动蛋白失稳。RNA干扰介导的TM5b的下调和过表达证实了其在AQP2的心尖转运中的抑制作用。这些发现表明了一种新的通道蛋白运输机制，在这种机制中，通道蛋白本身关键地调节局部肌动蛋白重组以启动其运动。
Trafficking of water channel aquaporin-2 (AQP2) to the apical membrane and its vasopressin and protein kinase A (PKA)–dependent regulation in renal collecting ducts is critical for body water homeostasis. We previously identified an AQP2 binding protein complex including actin and tropomyosin-5b (TM5b). We show that dynamic interactions between AQP2 and the actin cytoskeleton are critical for initiating AQP2 apical targeting. Specific binding of AQP2 to G-actin in reconstituted liposomes is negatively regulated by PKA phosphorylation. Dual color fluorescence cross-correlation spectroscopy reveals local AQP2 interaction with G-actin in live epithelial cells at single-molecule resolution. Cyclic adenosine monophosphate signaling and AQP2 phosphorylation release AQP2 from G-actin. In turn, AQP2 phosphorylation increases its affinity to TM5b, resulting in reduction of TM5b bound to F-actin, subsequently inducing F-actin destabilization. RNA interference–mediated knockdown and overexpression of TM5b confirm its inhibitory role in apical trafficking of AQP2. These findings indicate a novel mechanism of channel protein trafficking, in which the channel protein itself critically regulates local actin reorganization to initiate its movement.
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影响因子：
4.8
作者：
McCloskey, Diana T.;Doherty, Lynda;Yamboliev, Ilia A.
通讯作者：
Yamboliev, Ilia A.
DOI：
10.1152/ajprenal.1998.275.2.f285
发表时间：
1998-08-01
影响因子：
4.2
作者：
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通讯作者：
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作者：
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影响因子：
19.6
作者：
Asai, T;Kuwahara, M;Sasaki, S
通讯作者：
Sasaki, S
DOI：
10.1152/ajpgi.00065.2004
发表时间：
2004-10-01
影响因子：
4.5
作者：
Hopkins, AM;Bruewer, M;Nusrat, A
通讯作者：
Nusrat, A