Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
J Cell Sci 2021 Aug 15;13416:. doi: 10.1242/jcs.259013.
Show Gene links Show Anatomy links

A polycystin-2 protein with modified channel properties leads to an increased diameter of renal tubules and to renal cysts.

Grosch M , Brunner K , Ilyaskin AV , Schober M , Staudner T , Schmied D , Stumpp T , Schmidt KN , Madej MG , Pessoa TD , Othmen H , Kubitza M , Osten L , de Vries U , Mair MM , Somlo S , Moser M , Kunzelmann K , Ziegler C , Haerteis S , Korbmacher C , Witzgall R .

Mutations in the PKD2 gene cause autosomal-dominant polycystic kidney disease but the physiological role of polycystin-2, the protein product of PKD2, remains elusive. Polycystin-2 belongs to the transient receptor potential (TRP) family of non-selective cation channels. To test the hypothesis that altered ion channel properties of polycystin-2 compromise its putative role in a control circuit controlling lumen formation of renal tubular structures, we generated a mouse model in which we exchanged the pore loop of polycystin-2 with that of the closely related cation channel polycystin-2L1 (encoded by PKD2L1), thereby creating the protein polycystin-2poreL1. Functional characterization of this mutant channel in Xenopus laevis oocytes demonstrated that its electrophysiological properties differed from those of polycystin-2 and instead resembled the properties of polycystin-2L1, in particular regarding its permeability for Ca2+ ions. Homology modeling of the ion translocation pathway of polycystin-2poreL1 argues for a wider pore in polycystin-2poreL1 than in polycystin-2. In Pkd2poreL1 knock-in mice in which the endogenous polycystin-2 protein was replaced by polycystin-2poreL1 the diameter of collecting ducts was increased and collecting duct cysts developed in a strain-dependent fashion.

PubMed ID: 34345895
PMC ID: PMC8435292
Article link: J Cell Sci
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: calb1 dynll1 foxj1 nde1 pkd1 pkd2 pkd2l1
GO keywords: cation channel activity [+]

Disease Ontology terms: polycystic kidney disease [+]

Article Images: [+] show captions
References [+] :
Arif Pavel, Function and regulation of TRPP2 ion channel revealed by a gain-of-function mutant. 2016, Pubmed