A polycystin-2 protein with modified channel properties leads to an increased diameter of renal tubules and to renal cysts.
Xenopus laevis oocytes
Autosomal-dominant polycystic kidney disease
Electrophysiology
Knock-in mice
Lumen formation
PKD2
Polycystin-2
Tubular diameter
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
15 08 2021
15 08 2021
Historique:
received:
09
06
2021
accepted:
22
07
2021
pubmed:
5
8
2021
medline:
27
10
2021
entrez:
4
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34345895
pii: 271186
doi: 10.1242/jcs.259013
pmc: PMC8435292
pii:
doi:
Substances chimiques
Calcium Channels
0
Pkd2l1 protein, mouse
0
Receptors, Cell Surface
0
TRPP Cation Channels
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Informations de copyright
© 2021. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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