Abstract:
:Mutations in the polycystin genes, PKD1 or PKD2, 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 Pkd1 or Pkd2. 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 Ca2+, enhances its open probability. We introduce a novel method for measuring heterologous polycystin-2 channels in cilia, which will have utility in characterizing PKD2 variants that cause ADPKD.
journal_name
Elifejournal_title
eLifeauthors
Liu X,Vien T,Duan J,Sheu SH,DeCaen PG,Clapham DEdoi
10.7554/eLife.33183subject
Has Abstractpub_date
2018-02-14 00:00:00issn
2050-084Xpii
33183journal_volume
7pub_type
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