ArticleCell calcium2015
Both RyRs and TPCs are required for NAADP-induced intracellular Ca²⁺ release.
Article in Cell calcium, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
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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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024Pooled it
- Two-pore channel-2 controls calmodulin-dependent STIM1 inactivation.Nature communications · 2026Article
- Pancreatic acinar cell signalling and function exhibit an absolute requirement for activation of GαThe Journal of physiology · 2025Article
- Measuring NAADP-Evoked CaMethods in molecular biology (Clifton, N.J.) · 2025Article
- OCaR1 endows exocytic vesicles with autoregulatory competence by preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage.The Journal of clinical investigation · 2024Article
- The role of CaCell calcium · 2023Review
- Expanding the Toolbox: Novel Modulators of Endolysosomal Cation Channels.Handbook of experimental pharmacology · 2023Article
- Unexpected Motherhood-Triggered Hearing Loss in the Two-Pore Channel (TPC) Mutant Mouse.Biomedicines · 2022Article
- LRRK2 is required for CD38-mediated NAADP-CaAutophagy · 2022Article
- CD38 in the age of COVID-19: a medical perspective.Physiological reviews · 2021Review
- Lysosomal Calcium Channels in Autophagy and Cancer.Cancers · 2021Review
- Calcium Signaling in Pancreatic Immune CellsFunction (Oxford, England) · 2021Article
- NAADP: From Discovery to Mechanism.Frontiers in immunology · 2021Review
- Roles of NADMolecules (Basel, Switzerland) · 2020Review
- Targeting Two-Pore Channels: Current Progress and Future Challenges.Trends in pharmacological sciences · 2020Review
- CaCold Spring Harbor perspectives in biology · 2020Review
- Endocytic uptake of SARS-CoV-2: the critical roles of pH, CaFunction (Oxford, England) · 2020Article
- The Effects of Chloroquine and Hydroxychloroquine on ACE2-Related Coronavirus Pathology and the Cardiovascular System: An Evidence-Based Review.Function (Oxford, England) · 2020Article
- NAADP Receptors.Cold Spring Harbor perspectives in biology · 2019Review
- 5-Azido-8-ethynyl-NAADP: A bifunctional, clickable photoaffinity probe for the identification of NAADP receptors.Biochimica et biophysica acta. Molecular cell research · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Intracellular Ca(2+) release is mostly mediated by inositol trisphosphate, but intracellular cyclic-ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are important messengers in many systems. Whereas cADPR generally activates type 2 ryanodine receptors (RyR2s), the NAADP-activated Ca(2+) release mechanism is less clear. Using knockouts and antibodies against RyRs and Two-Pore Channels (TPCs), we have compared their relative importance for NAADP-induced Ca(2+) release from two-photon permeabilized pancreatic acinar cells. In these cells, cholecystokinin-elicited Ca(2+) release is mediated by NAADP. TPC2-KO reduced NAADP-induced Ca(2+) release by 64%, but the combination of TPC2-KO and an antibody against TPC1, significantly reduced Ca(2+) release by 86% (64% vs. 86%, p<0.0002). In RyR3-KO, NAADP-evoked Ca(2+) release reduced by ∼50% but, when combined with antibodies against RyR1, responses were 90% inhibited. Antibodies against RyR2 had practically no effect on NAADP-evoked Ca(2+) release, but reduced release in response to cADPR by 55%. Antibodies to RyR1 inhibited NAADP-induced Ca(2+) liberation by 81%, but only reduced cADPR responses by 30%. We conclude that full NAADP-mediated Ca(2+) release requires both TPCs and RyRs. The sequence of relative importance for NAADP-elicited Ca(2+) release from the all stores is RyR1>TPC2>RyR3>TPC1>>RyR2. However, when assessing NAADP-induced Ca(2+) release solely from the acidic stores (granules/endosomes/lysosomes), antibodies against TPC2 and TPC1 virtually abolished the Ca(2+) liberation as did antibodies against RyR1 and RyR3. Our results indicate that the primary, but very small, NAADP-elicited Ca(2+) release via TPCs from endosomes/lysosomes triggers the detectable Ca(2+)-induced Ca(2+) release via RyR1 and RyR3 occurring from the granules and the ER.
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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.