ArticleThe Journal of biological chemistry2012
Calcium-induced conformational changes in C-terminal tail of polycystin-2 are necessary for channel gating.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 50 citations in OpenAlex.
- 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
- Cardiovascular perspectives of the TRP channel polycystin 2.The Journal of physiology · 2024Article
- Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System.International journal of molecular sciences · 2023Review
- Ligand-induced conformational changes enable intersubunit communications in D-dopachrome tautomerase.Biophysical journal · 2023Article
- Role of PKD2 in the endoplasmic reticulum calcium homeostasis.Frontiers in physiology · 2022Review
- Polycystin-2 Is Required for Chondrocyte Mechanotransduction and Traffics to the Primary Cilium in Response to Mechanical Stimulation.International journal of molecular sciences · 2021Article
- Disrupting polycystin-2 EF hand CaJournal of cell science · 2020Article
- Polycystin 2: A calcium channel, channel partner, and regulator of calcium homeostasis in ADPKD.Cellular signalling · 2020Review
- Structure and function of polycystins: insights into polycystic kidney disease.Nature reviews. Nephrology · 2019Review
- TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells.Nature communications · 2019Article
- A mutation affecting polycystin-1 mediated heterotrimeric G-protein signaling causes PKD.Human molecular genetics · 2018Article
- Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels.Nature communications · 2018Article
- Global versus local mechanisms of temperature sensing in ion channels.Pflugers Archiv : European journal of physiology · 2018Review
- CaInternational journal of molecular sciences · 2018Review
- A Calmodulin C-Lobe CaNeuron · 2018Article
- Article
- Activation of the Calcium-Sensing Receptor Corrects the Impaired Mitochondrial Energy Status Observed in Renal Polycystin-1 Knockdown Cells Modeling Autosomal Dominant Polycystic Kidney Disease.Frontiers in molecular biosciences · 2018Article
- Polycystin and calcium signaling in cell death and survival.Cell calcium · 2018Review
- Structural studies of the C-terminal tail of polycystin-2 (PC2) reveal insights into the mechanisms used for the functional regulation of PC2.The Journal of physiology · 2016Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Polycystin-2 (PC2) is a Ca(2+)-permeable transient receptor potential channel activated and regulated by changes in cytoplasmic Ca(2+). PC2 mutations are responsible for ∼15% of autosomal dominant polycystic kidney disease. Although the C-terminal cytoplasmic tail of PC2 has been shown to contain a Ca(2+)-binding EF-hand domain, the molecular basis of PC2 channel gating by Ca(2+) remains unknown. We propose that the PC2 EF-hand is a Ca(2+) sensor required for channel gating. Consistent with this, Ca(2+) binding causes a dramatic decrease in the radius of gyration (R(g)) of the PC2 EF-hand by small angle x-ray scattering and significant conformational changes by NMR. Furthermore, increasing Ca(2+) concentrations cause the C-terminal cytoplasmic tail to transition from a mixture of extended oligomers to a single compact dimer by analytical ultracentrifugation, coupled with a >30 Å decrease in maximum interatomic distance (D(max)) by small angle x-ray scattering. Mutant PC2 channels unable to bind Ca(2+) via the EF-hand are inactive in single-channel planar lipid bilayers and inhibit Ca(2+) release from ER stores upon overexpression in cells, suggesting dominant negative properties. Our results support a model where PC2 channels are gated by discrete conformational changes in the C-terminal cytoplasmic tail in response to changes in cytoplasmic Ca(2+) levels. These properties of PC2 are lost in autosomal dominant polycystic kidney disease, emphasizing the importance of PC2 to kidney cell function. We speculate that PC2 and the Ca(2+)-dependent transient receptor potential channels in general are regulated by similar conformational changes in their cytoplasmic domains that are propagated to the channel pore.
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