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 A, Schober M, Staudner T, Schmied D, Stumpp T, Schmidt KN, Madej MG, Dantas Pessoa T, 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 (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 134

Article Number: jcs259013

Journal Issue: 16

DOI: 10.1242/jcs.259013

Abstract

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-2^poreL1. 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-2^poreL1 argues for a wider pore in polycystin-2^poreL1 than in polycystin-2. In Pkd2^poreL1 knock-in mice in which the endogenous polycystin-2 protein was replaced by polycystin-2^poreL1 the diameter of collecting ducts was increased and collecting duct cysts developed in a strain-dependent fashion.

Authors with CRIS profile

Additional Organisation(s)

Related research project(s)

Involved external institutions

Universität Regensburg Germany (DE) Yale University United States (USA) (US) Technische Universität München (TUM) Germany (DE)

How to cite

APA:

Grosch, M., Brunner, K., Ilyaskin, A., Schober, M., Staudner, T., Schmied, D.,... Witzgall, R. (2021). A polycystin-2 protein with modified channel properties leads to an increased diameter of renal tubules and to renal cysts. Journal of Cell Science, 134(16). https://doi.org/10.1242/jcs.259013

MLA:

Grosch, Melanie, et al. "A polycystin-2 protein with modified channel properties leads to an increased diameter of renal tubules and to renal cysts." Journal of Cell Science 134.16 (2021).

BibTeX: Download