Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor
Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor
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DOI：
10.1038/nature03650
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发表时间：
2005-06-30
期刊：
影响因子：
64.8
通讯作者：
Okamura, Y
中科院分区：
文献类型：
--
作者：
Murata, Y;Iwasaki, H;Okamura, Y
膜电位的变化影响离子通道和转运蛋白，从而改变细胞内的化学条件。已经提出了与膜电位偶联的其他信号传导途径（1-3），但其潜在机制尚不清楚。在这里，我们描述了一种新的蛋白质从海鞘玻璃海鞘，具有跨膜电压敏感结构域同源的S1 - S4段的电压门控通道和细胞质结构域类似的磷酸酶和张力蛋白同源物。这种蛋白质被命名为C。含钙离子电压传感器的磷酸酶（Ci-VSP）显示通道样的“门控”电流，并直接将膜电位的变化转化为磷酸肌醇的周转。Ci-VSP中磷酸肌醇磷酸酶的活性在膜电位的生理范围内调节。免疫细胞化学研究表明Ci-VSP在玻璃海鞘精子尾膜中表达，表明其可能在精子功能或形态中起作用。我们的数据表明，电压传感可以超越通道蛋白的功能，因此比以前实现的更普遍。
Changes in membrane potential affect ion channels and transporters, which then alter intracellular chemical conditions. Other signalling pathways coupled to membrane potential have been suggested(1-3) but their underlying mechanisms are unknown. Here we describe a novel protein from the ascidian Ciona intestinalis that has a transmembrane voltage-sensing domain homologous to the S1 - S4 segments of voltage-gated channels and a cytoplasmic domain similar to phosphatase and tensin homologue. This protein, named C. intestinalis voltage-sensor-containing phosphatase (Ci-VSP), displays channel-like 'gating' currents and directly translates changes in membrane potential into the turnover of phosphoinositides. The activity of the phosphoinositide phosphatase in Ci-VSP is tuned within a physiological range of membrane potential. Immunocytochemical studies show that Ci-VSP is expressed in Ciona sperm tail membranes, indicating a possible role in spermfunction or morphology. Our data demonstrate that voltage sensing can function beyond channel proteins and thus more ubiquitously than previously realized.