Murata Yoshimichi, Iwasaki Hirohide, Sasaki Mari, Inaba Kazuo, Okamura Yasushi
Section of Developmental Neurophysiology, Okazaki Institute for Integrative Bioscience, National Institutes of Natural Sciences, Higashiyama 5-1, Myodaiji-cho, Okazaki, Aichi, 444-8787, Japan.
Nature. 2005 Jun 30;435(7046):1239-43. doi: 10.1038/nature03650. Epub 2005 May 18.
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 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 sperm function or morphology. Our data demonstrate that voltage sensing can function beyond channel proteins and thus more ubiquitously than previously realized.
膜电位的变化会影响离子通道和转运体，进而改变细胞内的化学环境。虽然有人提出了与膜电位相关的其他信号通路，但其潜在机制尚不清楚。在这里，我们描述了一种来自海鞘（Ciona intestinalis）的新型蛋白质，它具有一个与电压门控通道的S1 - S4片段同源的跨膜电压感应结构域和一个类似于磷酸酶及张力蛋白同源物（phosphatase and tensin homologue）的胞质结构域。这种名为海鞘含电压传感器磷酸酶（C. intestinalis voltage-sensor-containing phosphatase，Ci-VSP）的蛋白质表现出类似通道的“门控”电流，并能将膜电位的变化直接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被调节。免疫细胞化学研究表明，Ci-VSP在海鞘精子尾膜中表达，这表明它在精子功能或形态方面可能发挥作用。我们的数据表明，电压感应不仅可以在通道蛋白中发挥作用，因此比之前所认识到的更为普遍。
