Tsiokas Leonidas, Kim Sehyun, Ong E-Ching
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States.
Cell Signal. 2007 Mar;19(3):444-53. doi: 10.1016/j.cellsig.2006.09.005. Epub 2006 Nov 3.
Naturally occurring mutations in two separate, but interacting loci, pkd1 and pkd2 are responsible for almost all cases of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is one of the most common genetic diseases resulting primarily in the formation of large kidney, liver, and pancreatic cysts. Homozygous deletion of either pkd1 or pkd2 results in embryonic lethality in mice due to kidney and heart defects illustrating their indispensable roles in mammalian development. However, the mechanism by which mutations in these genes cause ADPKD and other developmental defects are unknown. Research in the past several years has revealed that PKD2 has multiple functions depending on its subcellular localization. It forms a receptor-operated, non-selective cation channel in the plasma membrane, a novel intracellular Ca2+ release channel in the endoplasmic reticulum (ER), and a mechanosensitive channel in the primary cilium. This review focuses on the functional compartmentalization of PKD2, its modes of activation, and PKD2-mediated signal transduction.
两个独立但相互作用的基因座——多囊蛋白1（PKD1）和多囊蛋白2（PKD2）中的自然发生突变，几乎是所有常染色体显性多囊肾病（ADPKD）病例的病因。ADPKD是最常见的遗传病之一，主要导致肾脏、肝脏和胰腺形成大囊肿。PKD1或PKD2的纯合缺失会导致小鼠胚胎致死，原因是肾脏和心脏缺陷，这表明它们在哺乳动物发育中起着不可或缺的作用。然而，这些基因中的突变导致ADPKD和其他发育缺陷的机制尚不清楚。过去几年的研究表明，PKD2根据其亚细胞定位具有多种功能。它在质膜中形成一个受体操纵的非选择性阳离子通道，在内质网（ER）中形成一个新型的细胞内Ca2+释放通道，并在初级纤毛中形成一个机械敏感通道。本综述重点关注PKD2的功能分区、其激活模式以及PKD2介导的信号转导。
