ArticleProceedings of the National Academy of Sciences of the United States of America2014
Cyst formation following disruption of intracellular calcium signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 41 citations in OpenAlex.
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- Integrated metagenomics and transcriptomics analysis reveals pathways associated with oral periapical lesions formation and progression.Current research in microbial sciences · 2025Article
- Calcium signalling and transport in the kidney.Nature reviews. Nephrology · 2024Review
- Steady-state regulation of COPII-dependent secretory cargo sorting by inositol trisphosphate receptors, calcium, and penta EF hand proteins.The Journal of biological chemistry · 2023Article
- Polycystin-2-dependent transcriptome reveals early response of autosomal dominant polycystic kidney disease.Physiological genomics · 2023Article
- Calcium signaling in polycystic kidney disease- cell death and survival.Cell calcium · 2023Review
- Targeting the ADPKD methylome using nanoparticle-mediated combination therapy.APL bioengineering · 2023Article
- TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?International journal of molecular sciences · 2022Review
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- Polycystin 2: A calcium channel, channel partner, and regulator of calcium homeostasis in ADPKD.Cellular signalling · 2020Review
- Mitochondrial TRPC3 promotes cell proliferation by regulating the mitochondrial calcium and metabolism in renal polycystin-2 knockdown cells.International urology and nephrology · 2019Article
- Polycystin 2 regulates mitochondrial CaScience signaling · 2019Article
- Sensory primary cilium is a responsive cAMP microdomain in renal epithelia.Scientific reports · 2019Article
- Urinary proteome signature of Renal Cysts and Diabetes syndrome in children.Scientific reports · 2019Article
- Increased salt intake does not worsen the progression of renal cystic disease in high water-loaded PCK rats.PloS one · 2019Article
- Three-dimensional in vitro models answer the right questions in ADPKD cystogenesis.American journal of physiology. Renal physiology · 2018Review
- Insights into cellular and molecular basis for urinary tract infection in autosomal-dominant polycystic kidney disease.American journal of physiology. Renal physiology · 2017Review
- Rapamycin treatment dose-dependently improves the cystic kidney in a new ADPKD mouse model via the mTORC1 and cell-cycle-associated CDK1/cyclin axis.Journal of cellular and molecular medicine · 2017Article
- 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 2 institutions in 1 country.
Funding
Abstract
Mutations in polycystin 1 and 2 (PC1 and PC2) cause the common genetic kidney disorder autosomal dominant polycystic kidney disease (ADPKD). It is unknown how these mutations result in renal cysts, but dysregulation of calcium (Ca(2+)) signaling is a known consequence of PC2 mutations. PC2 functions as a Ca(2+)-activated Ca(2+) channel of the endoplasmic reticulum. We hypothesize that Ca(2+) signaling through PC2, or other intracellular Ca(2+) channels such as the inositol 1,4,5-trisphosphate receptor (InsP3R), is necessary to maintain renal epithelial cell function and that disruption of the Ca(2+) signaling leads to renal cyst development. The cell line LLC-PK1 has traditionally been used for studying PKD-causing mutations and Ca(2+) signaling in 2D culture systems. We demonstrate that this cell line can be used in long-term (8 wk) 3D tissue culture systems. In 2D systems, knockdown of InsP3R results in decreased Ca(2+) transient signals that are rescued by overexpression of PC2. In 3D systems, knockdown of either PC2 or InsP3R leads to cyst formation, but knockdown of InsP3R type 1 (InsP3R1) generated the largest cysts. InsP3R1 and InsP3R3 are differentially localized in both mouse and human kidney, suggesting that regional disruption of Ca(2+) signaling contributes to cystogenesis. All cysts had intact cilia 2 wk after starting 3D culture, but the cells with InsP3R1 knockdown lost cilia as the cysts grew. Studies combining 2D and 3D cell culture systems will assist in understanding how mutations in PC2 that confer altered Ca(2+) signaling lead to ADPKD cysts.
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