Polycystin-2 is an intracellular calcium release channel
Polycystin-2 is an intracellular calcium release channel
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DOI：
10.1038/ncb754
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发表时间：
2002-03-01
影响因子：
21.3
通讯作者：
Somlo, S
中科院分区：
文献类型：
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作者：
Koulen, P;Cai, YQ;Somlo, S
polycytin -2是2型常染色体显性多囊肾病（ADPKD）突变基因的产物，是瞬时受体电位（TRP）通道超家族亚家族的典型成员，在内质网（ER）膜中大量表达。在这里，我们通过单通道研究表明，多囊蛋白-2表现为钙激活的高电导内质网通道，可渗透到二价阳离子。过表达多囊蛋白-2的上皮细胞表现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或引入致病错义突变后丢失。这些数据表明，多囊蛋白-2在体内作为钙激活的细胞内钙释放通道发挥作用，多囊肾病是由于失去受调节的细胞内钙释放信号机制造成的。
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.