Calcium signaling and polycystin-2
Calcium signaling and polycystin-2
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DOI：
10.1016/j.bbrc.2004.08.043
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发表时间：
2004-10-01
影响因子：
3.1
通讯作者：
Ehrlich, BE
中科院分区：
文献类型：
--
作者：
Anyatonwu, GI;Ehrlich, BE
多囊肾病（PKD）是由两种基因PKD 1和PKD 2突变引起的，这两种基因分别编码多囊蛋白-1（PC 1）和多囊蛋白-2（PC 2）。虽然已经在这两种蛋白质中鉴定出疾病相关突变，但导致临床症状的分子事件序列仍然未知。PC 1存在于质膜中，并且被认为在细胞-细胞和细胞-基质相互作用中起作用，而PC 2是集中在内质网中的钙（Ca 2+）可渗透阳离子通道。这两种蛋白定位于初级纤毛，在那里它们作为机械敏感性受体复合物起作用，允许Ca 2+进入细胞。下游信号通路涉及细胞内Ca 2+释放通道的激活，特别是Ryanodine受体（RyR），但后续步骤仍有待确定。阐明参与正常PC 1/PC 2功能的信号通路、PC 1/PC 2突变的功能后果以及Ca 2+信号通路的作用都将有助于阐明PKD囊肿发生的分子机制。(C)2004年爱思唯尔公司All rights reserved.
Polycystic kidney disease (PKD) is caused by mutations in two genes, PKD1 and PKD2, which encode for the proteins, polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Although disease-associated mutations have been identified in these two proteins, the sequence of molecular events leading up to clinical symptoms is still unknown. PC1 resides in the plasma membrane and it is thought to function in cell-cell and cell-matrix interactions, whereas PC2 is a calcium (Ca2+) permeable cation channel concentrated in the endoplasmic reticulum. Both proteins localize to the primary cilia where they function as a mechanosensitive receptor complex allowing the entry of Ca2+ into the cell. The downstream signaling pathway involves activation of intracellular Ca2+ release channels, especially the ryanodine receptor (RyR), but subsequent steps are still to be identified. Elucidation of the signaling pathway involved in normal PC1/PC2 function, the functional consequences of PC1/PC2 mutation, and the role of Ca2+ signaling will all help to unravel the molecular mechanisms of cystogenesis in PKD. (C) 2004 Elsevier Inc. All rights reserved.