ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
The number and location of EF hand motifs dictates the calcium dependence of polycystin-2 function.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Calcium signaling in polycystic kidney disease- cell death and survival.Cell calcium · 2023Review
- Article
- Article
- Polycystins as components of large multiprotein complexes of polycystin interactors.Cellular signalling · 2020Review
- 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
- Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels.Nature communications · 2018Article
- Structure of the polycystic kidney disease TRP channel Polycystin-2 (PC2).Nature structural & molecular biology · 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
- Function and regulation of TRPP2 ion channel revealed by a gain-of-function mutant.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Conformational dynamics of Ca2+-dependent responses in the polycystin-2 C-terminal tail.The Biochemical journal · 2016Article
- Oligomerization of the polycystin-2 C-terminal tail and effects on its Ca2+-binding properties.The Journal of biological chemistry · 2015Article
- Cyst formation following disruption of intracellular calcium signaling.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Polycystin 2 (PC2) is a calcium-dependent calcium channel, and mutations to human PC2 (hPC2) are associated with polycystic kidney disease. The C-terminal tail of hPC2 contains 2 EF hand motifs, but only the second binds calcium. Here, we investigate whether these EF hand motifs serve as a calcium sensor responsible for the calcium dependence of PC2 function. Using NMR and bioinformatics, we show that the overall fold is highly conserved, but in evolutionarily earlier species, both EF hands bind calcium. To test whether the EF hand motif is truly a calcium sensor controlling PC2 channel function, we altered the number of calcium binding sites in hPC2. NMR studies confirmed that modified hPC2 binds an additional calcium ion. Single-channel recordings demonstrated a leftward shift in the calcium dependence, and imaging studies in cells showed that calcium transients were enhanced compared with wild-type hPC2. However, biophysics and functional studies showed that the first EF hand can only bind calcium and be functionally active if the second (native) calcium-binding EF hand is intact. These results suggest that the number and location of calcium-binding sites in the EF hand senses the concentration of calcium required for PC2 channel activity and cellular function.
Indexed as
Identifiers
What OpenQuestion holds
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.