Department of Cardiology, Howard Hughes Medical Institute, Boston Children's Hospital, Boston, United States.
Department of Neurobiology, Harvard Medical School, Boston, United States.
Elife. 2018 Feb 14;7:e33183. doi: 10.7554/eLife.33183.
Mutations in the polycystin genes, or results in Autosomal Dominant Polycystic Kidney Disease (ADPKD). Although a genetic basis of ADPKD is established, we lack a clear understanding of polycystin proteins' functions as ion channels. This question remains unsolved largely because polycystins localize to the primary cilium - a tiny, antenna-like organelle. Using a new ADPKD mouse model, we observe primary cilia that are abnormally long in cells associated with cysts after conditional ablation of or . Using primary cultures of collecting duct cells, we show that polycystin-2, but not polycystin-1, is a required subunit for the ion channel in the primary cilium. The polycystin-2 channel preferentially conducts K and Na; intraciliary Ca, enhances its open probability. We introduce a novel method for measuring heterologous polycystin-2 channels in cilia, which will have utility in characterizing variants that cause ADPKD.
多囊蛋白基因的突变，或导致常染色体显性多囊肾病（ADPKD）。尽管 ADPKD 的遗传基础已经确立，但我们对多囊蛋白作为离子通道的功能仍缺乏清晰的认识。这个问题尚未解决，主要是因为多囊蛋白定位于初级纤毛——一种微小的、天线状的细胞器。使用一种新的 ADPKD 小鼠模型，我们观察到在条件性敲除 或 后，与囊肿相关的细胞中的初级纤毛异常伸长。通过收集管细胞的原代培养，我们表明多囊蛋白-2 而不是多囊蛋白-1 是初级纤毛中离子通道的必需亚基。多囊蛋白-2 通道优先传导 K 和 Na；胞内 Ca 增加其开放概率。我们引入了一种测量纤毛中异源多囊蛋白-2 通道的新方法，该方法将有助于表征导致 ADPKD 的 变体。
