| First Author | Grosch M | Year | 2021 |
| Journal | J Cell Sci | Volume | 134 |
| Issue | 16 | PubMed ID | 34345895 |
| Mgi Jnum | J:327006 | Mgi Id | MGI:6849621 |
| Doi | 10.1242/jcs.259013 | Citation | Grosch M, et al. (2021) A polycystin-2 protein with modified channel properties leads to an increased diameter of renal tubules and to renal cysts. J Cell Sci 134(16):jcs259013 |
| abstractText | 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. |
