ArticleScience signaling2016
Defining the stoichiometry of inositol 1,4,5-trisphosphate binding required to initiate Ca2+ release.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 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
101 citing papers in PubMed.
- Carbonic anhydrase VIII regulates IP3R1-dependent CaScience advances · 2026Article
- Cryo-EM insights into isoform-specific properties of the IPNature communications · 2026Article
- Two-pore channel-2 controls calmodulin-dependent STIM1 inactivation.Nature communications · 2026Article
- An INF2-dependent actin-mediated step in inositol 1,4,5-trisphosphate receptor cluster formation and activity.Current biology : CB · 2026Article
- Conformational landscape and ligand-dependent clustering of the human type 2 IPNature communications · 2026Article
- Pacemaking in the lymphatic system.The Journal of physiology · 2026Review
- Latrophilin-1-Mediated GCells · 2026Article
- Expanding the Early Childhood Manifestations ofNeurology. Genetics · 2026Article
- Structural dynamics of adenine nucleotide potentiation of the human type 2 IPbioRxiv : the preprint server for biology · 2026Article
- Article
- Pancreatic acinar cell signalling and function exhibit an absolute requirement for activation of GαThe Journal of physiology · 2025Article
- From IP3RPEP6 Inhibition of IPCellular and molecular life sciences : CMLS · 2025Review
- IP3 receptor depletion in a spontaneous canine model of Charcot-Marie-Tooth disease 1J with amelogenesis imperfecta.PLoS genetics · 2025Article
- Simultaneous detection of membrane contact dynamics and associated CaNature communications · 2024Article
- A pleiotropic recurrent dominantScience advances · 2024Article
- A structure-based computational model of IPBiophysical journal · 2024Article
- Agonist-Induced CaCells · 2024Article
- Relevance of the endoplasmic reticulum-mitochondria axis in cancer diagnosis and therapy.Experimental & molecular medicine · 2024Review
- Two-pore channel-2 and inositol trisphosphate receptors coordinate CaCell reports · 2024Article
- Calcium signaling in oocyte quality and functionality and its application.Frontiers in endocrinology · 2024Review
41 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are tetrameric intracellular Ca(2+)-release channels with each subunit containing a binding site for IP3in the amino terminus. We provide evidence that four IP3molecules are required to activate the channel under diverse conditions. Comparing the concentration-response relationship for binding and Ca(2+)release suggested that IP3Rs are maximally occupied by IP3before substantial Ca(2+)release occurs. We showed that ligand binding-deficient subunits acted in a dominant-negative manner when coexpressed with wild-type monomers in the chicken immune cell line DT40-3KO, which lacks all three genes encoding IP3R subunits, and confirmed the same effect in an IP3R-null human cell line (HEK-3KO) generated by CRISPR/Cas9 technology. Using dimeric and tetrameric concatenated IP3Rs with increasing numbers of binding-deficient subunits, we addressed the obligate ligand stoichiometry. The concatenated IP3Rs with four ligand-binding sites exhibited Ca(2+)release and electrophysiological properties of native IP3Rs. However, IP3failed to activate IP3Rs assembled from concatenated dimers consisting of one binding-competent and one binding-deficient mutant subunit. Similarly, IP3Rs containing two monomers of IP3R2short, an IP3binding-deficient splice variant, were nonfunctional. Concatenated tetramers containing only three binding-competent ligand-binding sites were nonfunctional under a wide range of activating conditions. These data provide definitive evidence that IP3-induced Ca(2+)release only occurs when each IP3R monomer within the tetramer is occupied by IP3, thereby ensuring fidelity of Ca(2+)release.
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.