多囊蛋白-2是一种细胞内钙释放通道。

Polycystin-2 is an intracellular calcium release channel.

作者信息

Koulen Peter, Cai Yiqiang, Geng Lin, Maeda Yoshiko, Nishimura Sayoko, Witzgall Ralph, Ehrlich Barbara E, Somlo Stefan

机构信息

Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.

出版信息

Nat Cell Biol. 2002 Mar;4(3):191-7. doi: 10.1038/ncb754.

DOI:10.1038/ncb754

PMID:11854751

Abstract

Polycystin-2, the product of the gene mutated in type 2 autosomal dominant polycystic kidney disease (ADPKD), is the prototypical member of a subfamily of the transient receptor potential (TRP) channel superfamily, which is expressed abundantly in the endoplasmic reticulum (ER) membrane. Here, we show by single channel studies that polycystin-2 behaves as a calcium-activated, high conductance ER channel that is permeable to divalent cations. Epithelial cells overexpressing polycystin-2 show markedly augmented intracellular calcium release signals that are lost after carboxy-terminal truncation or by the introduction of a disease-causing missense mutation. These data suggest that polycystin-2 functions as a calcium-activated intracellular calcium release channel in vivo and that polycystic kidney disease results from the loss of a regulated intracellular calcium release signalling mechanism.

摘要

多囊蛋白-2是2型常染色体显性多囊肾病（ADPKD）中发生突变的基因的产物，是瞬时受体电位（TRP）通道超家族一个亚家族的典型成员，在内质网（ER）膜中大量表达。在此，我们通过单通道研究表明，多囊蛋白-2表现为一种钙激活的、高电导的内质网通道，对二价阳离子具有通透性。过表达多囊蛋白-2的上皮细胞显示出明显增强的细胞内钙释放信号，这些信号在羧基末端截断后或引入致病错义突变后消失。这些数据表明，多囊蛋白-2在体内作为一种钙激活的细胞内钙释放通道发挥作用，多囊肾病是由受调控的细胞内钙释放信号机制丧失所致。