Evolutionary conservation of Drosophila polycystin-2 as a calcium-activated cation channel.-猫眼课题宝

果蝇多囊蛋白-2 作为钙激活阳离子通道的进化保护。

DOI：

10.1097/01.asn.0000125616.42669.51

发表时间：

2004

期刊：

Journal of the American Society of Nephrology : JASN

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

Venglarik,CharlesJ;Gao,Zhiqian;Lu,Xiangyi

PKD 2基因突变导致人类常染色体显性多囊肾病（ADPKD）。PKD 2编码的蛋白质与电压敏感性阳离子通道和TRP通道相似，被命名为多囊蛋白-2（PC 2）。与此结构信息一致，表达的PC 2在非洲爪蟾卵母细胞或重建的人PC 2在平面脂质双层产生Ca 2+激活的阳离子通道。尽管这些研究提供了PC 2诱导通道的生物物理、调节和药理学特性的基本描述，但仍不清楚缺陷的PC 2活性如何导致ADPKD患者的囊肿形成和扩张。为了建立研究PC 2功能和调控的遗传模型，作者鉴定并克隆了果蝇PC 2（DmPC 2）。这里显示DmPKD 2在果蝇S2细胞中的表达产生了新的通道。在此通道的属性的哺乳动物PKD 2诱导的通道的相似性的基础上，这果蝇通道预计将提供一个方便的遗传模型解剖ADPKD的机制。

Mutations in the PKD2 gene cause autosomal dominant polycystic kidney disease (ADPKD) in humans. The protein encoded by PKD2 has similarity to voltage-sensitive cation channels and TRP channels and was named polycystin-2 (PC2). In agreement with this structural information, expression of PC2 in Xenopus oocytes or reconstitution of human PC2 in planar lipid bilayers produced Ca 2+-activated cation channels. Although these studies provided a basic description of the biophysical, regulatory, and pharmacologic properties of the PC2-induced channels, it is still unknown how defective PC2 activity leads to cyst formation and expansion in ADPKD patients. To establish a genetic model for studying PC2 function and regulation, the authors identified and cloned a Drosophila PC2 (DmPC2). It is here shown that expression of DmPKD2 in Drosophila S2 cells produced a novel channel. On the basis of the similarity of this channel’s properties to mammalian PKD2-induced channels, this Drosophila channel is expected to provide a convenient genetic model for dissecting the mechanisms underlying ADPKD.