Depletion of intracellular Ca2+ stores stimulates the translocation of vanilloid transient receptor potential 4-c1 heteromeric channels to the plasma membrane.
Depletion of intracellular Ca2+ stores stimulates the translocation of vanilloid transient receptor potential 4-c1 heteromeric channels to the plasma membrane.
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DOI：
10.1161/atvbaha.110.212084
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Yao X
中科院分区：
文献类型：
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作者：
Ma X;Cao J;Luo J;Nilius B;Huang Y;Ambudkar IS;Yao X
研究钙库耗竭对香草素瞬时受体电位（TRPV）4-C1通道向质膜转位的影响。囊泡运输是控制TRP通道在质膜中表面表达的关键机制，TRP通道在质膜中执行其功能。体内TRP通道通常由异聚亚基组成。使用全内荧光反射显微镜和生物素表面标记的实验表明，Ca 2+库耗竭增强TRPV 4-C1在与TRPV 4和典型瞬时受体电位1（TRPC 1）共表达的人胚肾293细胞中向质膜的易位。荧光Ca ~（2+）测量和膜片钳研究表明，Ca ~（2+）库耗竭增强了4α-PDD刺激的Ca ~（2+）内流和阳离子电流。易位需要基质相互作用分子1（STIM 1）。TRPV 4-C1异聚体通道比TRPC 1或TRPV 4同源体通道更有利地易位到质膜。在天然血管内皮细胞中获得了类似的结果。Ca 2+库耗竭刺激TRPV 4-C1异聚体通道插入质膜，导致响应于人胚肾细胞过表达系统和天然内皮细胞中的流动而增加的Ca 2+内流。
To examine the effect of Ca2+ store depletion on the translocation of vanilloid transient receptor potential (TRPV) 4-C1 heteromeric channels to the plasma membrane. Vesicular trafficking is a key mechanism for controlling the surface expression of TRP channels in the plasma membrane, where they perform their function. TRP channels in vivo are often composed of heteromeric subunits. Experiments using total internal fluorescence reflection microscopy and biotin surface labeling show that Ca2+ store depletion enhanced TRPV4-C1 translocation into the plasma membrane in human embryonic kidney 293 cells that were coexpressed with TRPV4 and canonical transient receptor potential 1 (TRPC1). Fluorescent Ca2+ measurement and patch clamp studies demonstrated that Ca2+ store depletion enhanced 4α-PDD–stimulated Ca2+ influx and cation current. The translocation required stromal interacting molecule 1 (STIM1). TRPV4-C1 heteromeric channels were more favorably translocated to the plasma membrane than TRPC1 or TRPV4 homomeric channels. Similar results were obtained in native vascular endothelial cells. Ca2+ store depletion stimulates the insertion of TRPV4-C1 heteromeric channels into the plasma membrane, resulting in an augmented Ca2+ influx in response to flow in the human embryonic kidney cell overexpression system and native endothelial cells.