ArticleNature2009
NAADP mobilizes calcium from acidic organelles through two-pore channels.
Article in Nature, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 455 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
455 citing papers in PubMed, 1 synthesis or guideline pooled it, 743 citations in OpenAlex.
- The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019Pooled it
- Local calcium dynamics and signalling in cardiomyocytes.Nature reviews. Cardiology · 2026Review
- Inhibition of endolysosomal two-pore channel 2 (TPC2) induces osteoblast differentiation and matrix mineralization while targeting autophagy.Journal of endocrinological investigation · 2026Article
- Allosteric switching of CaThe EMBO journal · 2026Article
- Lysosomal channel TPC2 modulates microglia-endothelial signaling in choroidal angiogenesis.Angiogenesis · 2026Article
- Endosomal TPC1-mediated CaProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Endolysosomal two-pore channels regulate a conserved entry pathway for enteroviruses.The Journal of general virology · 2026Article
- Two-pore channel-2 controls calmodulin-dependent STIM1 inactivation.Nature communications · 2026Article
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- Review
- Voltage-gated proton channel Hv1/VSOP regulates reciprocal interactions between F-actin and endosomes in microglia.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- NAADP elicits two-pore channel currents by lifting Lsm12-mediated inhibition of PI(3,5)PbioRxiv : the preprint server for biology · 2026Article
- Macrophage metabolic exhaustion and PANoptotic cell death drive chronic tissue inflammation in rheumatoid arthritis.Immunity · 2026Article
- Review
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Activation of TPC2 amplifies lysosome-mitochondria calcium transfer to regulate energetic stress responses.bioRxiv : the preprint server for biology · 2026Article
- GluN2A-mediated currents and calcium signal in human iPSC-derived neurons.Scientific reports · 2026Article
- Review
- Inactive ryanodine receptors sustain lysosomal availability for autophagy by promoting ER-lysosomal contact site formation.Nature communications · 2026Article
- Liquid liquid phase separation of the intrinsically disordered protein JPT2 compartmentalizes components of NAADP-evoked CabioRxiv : the preprint server for biology · 2026Article
395 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
21 authors at 6 institutions in 3 countries.
Funding
Abstract
Ca(2+) mobilization from intracellular stores represents an important cell signalling process that is regulated, in mammalian cells, by inositol-1,4,5-trisphosphate (InsP(3)), cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate (NAADP). InsP(3) and cyclic ADP ribose cause the release of Ca(2+) from sarcoplasmic/endoplasmic reticulum stores by the activation of InsP(3) and ryanodine receptors (InsP(3)Rs and RyRs). In contrast, the nature of the intracellular stores targeted by NAADP and the molecular identity of the NAADP receptors remain controversial, although evidence indicates that NAADP mobilizes Ca(2+) from lysosome-related acidic compartments. Here we show that two-pore channels (TPCs) comprise a family of NAADP receptors, with human TPC1 (also known as TPCN1) and chicken TPC3 (TPCN3) being expressed on endosomal membranes, and human TPC2 (TPCN2) on lysosomal membranes when expressed in HEK293 cells. Membranes enriched with TPC2 show high affinity NAADP binding, and TPC2 underpins NAADP-induced Ca(2+) release from lysosome-related stores that is subsequently amplified by Ca(2+)-induced Ca(2+) release by InsP(3)Rs. Responses to NAADP were abolished by disrupting the lysosomal proton gradient and by ablating TPC2 expression, but were only attenuated by depleting endoplasmic reticulum Ca(2+) stores or by blocking InsP(3)Rs. Thus, TPCs form NAADP receptors that release Ca(2+) from acidic organelles, which can trigger further Ca(2+) signals via sarcoplasmic/endoplasmic reticulum. TPCs therefore provide new insights into the regulation and organization of Ca(2+) signals in animal cells, and will advance our understanding of the physiological role of NAADP.
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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.