ArticleeLife2020
The heteromeric PC-1/PC-2 polycystin complex is activated by the PC-1 N-terminus.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 76 citations in OpenAlex.
- PKD2-like proteins targetProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- Structural basis of lipid-dependent allosteric gating mechanisms for PC1-PC2 ion channel.Nature communications · 2026Article
- Polycystin-1 and Cardiac Remodeling: From Mechanotransduction to Clinical Consequences.Circulation research · 2026Review
- Advances in the Treatment of Autosomal Dominant Polycystic Kidney Disease and Novel Therapeutic Targets.Current issues in molecular biology · 2026Review
- A heteromeric TRP channel that functions as a WNT-activated G protein-coupled receptor.Nature communications · 2026Article
- Molecular pathology and cystogenic propensity of the ADPKD Taiwan founder variant.JCI insight · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Cleavage of N-terminus of polycystin-1 increases calcium permeability of polycystin-1/2 receptor channel complexes.JCI insight · 2025Article
- Defining the polycystin pharmacophore through high-throughput screening and computational biophysics.British journal of pharmacology · 2025Article
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Kidney organoid models of polycystic kidney disease: challenges and future directions.American journal of physiology. Renal physiology · 2025Review
- Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease: Role in Cystogenesis and Novel Therapeutic Approaches.Biomedicines · 2025Review
- Pathogenic variants in the polycystin pore helix cause distinct forms of channel dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Ion channel function of polycystin-2/polycystin-1 heteromer revealed by structure-guided mutagenesis.FEBS letters · 2025Article
- Polycystins recruit cargo to distinct ciliary extracellular vesicle subtypes in C. elegans.Nature communications · 2025Article
- Review
- Hyperosmolality activates polycystin-2 and TRPM4 in renal primary cilium.Pflugers Archiv : European journal of physiology · 2025Article
- Identification of polycystin 2 missense mutants targeted for endoplasmic reticulum-associated degradation.American journal of physiology. Cell physiology · 2025Article
- The mutual interaction of TRPC5 channel with polycystin proteins.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the polycystin proteins, PC-1 and PC-2, result in autosomal dominant polycystic kidney disease (ADPKD) and ultimately renal failure. PC-1 and PC-2 enrich on primary cilia, where they are thought to form a heteromeric ion channel complex. However, a functional understanding of the putative PC-1/PC-2 polycystin complex is lacking due to technical hurdles in reliably measuring its activity. Here we successfully reconstitute the PC-1/PC-2 complex in the plasma membrane of mammalian cells and show that it functions as an outwardly rectifying channel. Using both reconstituted and ciliary polycystin channels, we further show that a soluble fragment generated from the N-terminal extracellular domain of PC-1 functions as an intrinsic agonist that is necessary and sufficient for channel activation. We thus propose that autoproteolytic cleavage of the N-terminus of PC-1, a hotspot for ADPKD mutations, produces a soluble ligand in vivo. These findings establish a mechanistic framework for understanding the role of PC-1/PC-2 heteromers in ADPKD and suggest new therapeutic strategies that would expand upon the limited symptomatic treatments currently available for this progressive, terminal disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.