Potential role of voltage-sensing phosphatases in regulation of cell structure through the production of PI(3,4)P2
Potential role of voltage-sensing phosphatases in regulation of cell structure through the production of PI(3,4)P2
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电压感应磷酸酶通过产生 PI(3,4)P2 调节细胞结构的潜在作用
DOI：
10.1002/jcp.24463
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Okamura Y & Homma KJ
中科院分区：
文献类型：
--
作者：
Yamaguchi S;Kurokawa T;Taira I;Aoki N;Sakata S;Okamura Y & Homma KJ
电压敏感磷酸酶（VSP）由作为电压传感器的跨膜结构域和具有磷酸肌醇磷酸酶活性的胞质结构域组成。电压传感器与细胞质磷酸酶紧密偶联，膜去极化诱导几种磷酸肌醇的去磷酸化。VSP基因是从尾索动物到人类的保守基因。VSP同源蛋白之间、电压传感器运动的电压范围以及底物选择性存在一些差异。与最近的理解的生物物理机制的VSP，鲜为人知的是，它的生理作用。在这里，我们报告了VSP的鸡直系同源物（指定为Gg-VSP）在其强制表达后诱导DF-1成纤维细胞中具有圆形细胞体的细胞突起生长的形态学特征。电压传感器突变体Gg-VSPR 153 Q的表达与电压依赖性转移到较低电压相比，导致细胞形态的变化更频繁。共表达使PI（3，4）P2去磷酸化的PTEN抑制了Gg-VSP的这种作用，表明PI（3，4）P2的增加导致细胞形状的改变。此外，用与TAPP 1衍生的普列克底物蛋白同源性（PH）结构域融合的荧光蛋白对PI（3，4）P2的可视化表明Gg-VSP影响PI（3，4）P2的分布。这些发现提出了一种可能性，即VSP的功能之一可能是通过对磷酸肌醇谱的电压敏感性调节来调节细胞形态。J.细胞。229：422-433，2014。© 2013 Wiley Periodicals，Inc.
Voltage‐sensing phosphatase, VSP, consists of the transmembrane domain, operating as the voltage sensor, and the cytoplasmic domain with phosphoinositide‐phosphatase activities. The voltage sensor tightly couples with the cytoplasmic phosphatase and membrane depolarization induces dephosphorylation of several species of phosphoinositides. VSP gene is conserved from urochordate to human. There are some diversities among VSP ortholog proteins; range of voltage of voltage sensor motions as well as substrate selectivity. In contrast with recent understandings of biophysical mechanisms of VSPs, little is known about its physiological roles. Here we report that chick ortholog of VSP (designated as Gg‐VSP) induces morphological feature of cell process outgrowths with round cell body in DF‐1 fibroblasts upon its forced expression. Expression of the voltage sensor mutant, Gg‐VSPR153Qwith shifted voltage dependence to a lower voltage led to more frequent changes of cell morphology than the wild‐type protein. Coexpression of PTEN that dephosphorylates PI(3,4)P2suppressed this effect by Gg‐VSP, indicating that the increase of PI(3,4)P2leads to changes of cell shape. In addition, visualization of PI(3,4)P2with the fluorescent protein fused with the TAPP1‐derived pleckstrin homology (PH) domain suggested that Gg‐VSP influenced the distribution of PI(3,4)P2. These findings raise a possibility that one of the VSP's functions could be to regulate cell morphology through voltage‐sensitive tuning of phosphoinositide profile. J. Cell. Physiol. 229: 422–433, 2014. © 2013 Wiley Periodicals, Inc.