ArticleProceedings of the National Academy of Sciences of the United States of America2001
Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 1 of them a synthesis that pooled it.
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179 citing papers in PubMed, 1 synthesis or guideline pooled it, 444 citations in OpenAlex.
- Integrative Genome-Wide Association Studies of eQTL and GWAS Data for Gout Disease Susceptibility.Scientific reports · 2019Pooled it
- Proteomic Analysis of Effects of Spironolactone in Heart Failure With Preserved Ejection Fraction.Circulation. Heart failure · 2022Trial
- Age-associated changes in the shell gland transcriptomics and eggshell quality of broiler breeder hens.BMC genomics · 2026Article
- Functional Coupling of Calcium-Sensing Receptor and Polycystin-2 in Renal Epithelial Cells: Physiological Role and Potential Therapeutic Target in Polycystic Kidney Disease.International journal of molecular sciences · 2025Article
- Cleavage of N-terminus of polycystin-1 increases calcium permeability of polycystin-1/2 receptor channel complexes.JCI insight · 2025Article
- Identification of polycystin 2 missense mutants targeted for endoplasmic reticulum-associated degradation.American journal of physiology. Cell physiology · 2025Article
- Tolvaptan safety in autosomal-dominant polycystic kidney disease; a focus on idiosyncratic drug-induced liver injury liabilities.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Review
- Molecular and structural basis of the dual regulation of the polycystin-2 ion channel by small-molecule ligands.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Autosomal Dominant Polycystic Kidney Disease: Extrarenal Involvement.International journal of molecular sciences · 2024Review
- Altered placental ion channel gene expression in preeclamptic high-altitude pregnancies.Physiological genomics · 2023Article
- Co-Inheritance of Pathogenic Variants inGenes · 2023Article
- Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System.International journal of molecular sciences · 2023Review
- Smooth muscle cells, interstitial cells and neurons in the gallbladder (GB): Functional syncytium of electrical rhythmicity and GB motility (Review).International journal of molecular medicine · 2023Review
- Placental ion channels: potential target of chemical exposure.Biology of reproduction · 2023Review
- Role of the microtubules in the electrical activity of the primary cilium of renal epithelial cells.Frontiers in molecular biosciences · 2023Article
- Membrane stretching activates calcium permeability of a putative channel Pkd2 during fission yeast cytokinesis.Molecular biology of the cell · 2022Article
- Kidney stone formation in a novel murine model of polycystic kidney disease.American journal of physiology. Renal physiology · 2022Article
- Fission yeast polycystin Pkd2p promotes cell size expansion and antagonizes the Hippo-related SIN pathway.Journal of cell science · 2022Article
- TRP Channels as Molecular Targets to Relieve Endocrine-Related Diseases.Frontiers in molecular biosciences · 2022Review
119 more citing papers are in PubMed but not listed here.
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10 authors at 2 institutions in 1 country.
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Abstract
Defects in polycystin-2, a ubiquitous transmembrane glycoprotein of unknown function, is a major cause of autosomal dominant polycystic kidney disease (ADPKD), whose manifestation entails the development of fluid-filled cysts in target organs. Here, we demonstrate that polycystin-2 is present in term human syncytiotrophoblast, where it behaves as a nonselective cation channel. Lipid bilayer reconstitution of polycystin-2-positive human syncytiotrophoblast apical membranes displayed a nonselective cation channel with multiple subconductance states, and a high perm-selectivity to Ca2+. This channel was inhibited by anti-polycystin-2 antibody, Ca2+, La3+, Gd3+, and the diuretic amiloride. Channel function by polycystin-2 was confirmed by patch-clamping experiments of polycystin-2 heterologously infected Sf9 insect cells. Further, purified insect cell-derived recombinant polycystin-2 and in vitro translated human polycystin-2 had similar ion channel activity. The polycystin-2 channel may be associated with fluid accumulation and/or ion transport regulation in target epithelia, including placenta. Dysregulation of this channel provides a mechanism for the onset and progression of ADPKD.
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