ArticleThe EMBO journal2015
Expression of Ca²⁺-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019Pooled it
- NagX, a periplasmic β-Antimicrobial agents and chemotherapy · 2026Article
- Endosomal TPC1-mediated CaProceedings of the National Academy of Sciences of the United States of America · 2026Article
- O-linked glycan-dependent gating of TPC2 controls lysosomal excitability and organelle remodeling.Nature communications · 2026Article
- NAADP elicits two-pore channel currents by lifting Lsm12-mediated inhibition of PI(3,5)PbioRxiv : the preprint server for biology · 2026Article
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- TPC2: From Blond Hair to Melanoma?Cancers · 2024Review
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- The ion channels of endomembranes.Physiological reviews · 2024Review
- Pathological Functions of Lysosomal Ion Channels in the Central Nervous System.International journal of molecular sciences · 2024Review
- Two-pore channels regulate endomembrane tension to enable remodeling and resolution of phagolysosomes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Time-resolved role of P2X4 and P2X7 during CD8Frontiers in immunology · 2024Article
- Two-pore channel regulators - Who is in control?Frontiers in physiology · 2024Review
- Convergent activation of CaScience signaling · 2023Article
- Convergent activation of two-pore channels mediated by the NAADP-binding proteins JPT2 and LSM12.Science signaling · 2023Article
- Lysosomal calcium loading promotes spontaneous calcium release by potentiating ryanodine receptors.Biophysical journal · 2023Article
- Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structure and Function of Plant and Mammalian TPC Channels.Handbook of experimental pharmacology · 2023Article
- Characterization of Endo-Lysosomal Cation Channels Using Calcium Imaging.Handbook of experimental pharmacology · 2023Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
The second messenger NAADP triggers Ca(2+) release from endo-lysosomes. Although two-pore channels (TPCs) have been proposed to be regulated by NAADP, recent studies have challenged this. By generating the first mouse line with demonstrable absence of both Tpcn1 and Tpcn2 expression (Tpcn1/2(-/-)), we show that the loss of endogenous TPCs abolished NAADP-dependent Ca(2+) responses as assessed by single-cell Ca(2+) imaging or patch-clamp of single endo-lysosomes. In contrast, currents stimulated by PI(3,5)P2 were only partially dependent on TPCs. In Tpcn1/2(-/-) cells, NAADP sensitivity was restored by re-expressing wild-type TPCs, but not by mutant versions with impaired Ca(2+)-permeability, nor by TRPML1. Another mouse line formerly reported as TPC-null likely expresses truncated TPCs, but we now show that these truncated proteins still support NAADP-induced Ca(2+) release. High-affinity [(32)P]NAADP binding still occurs in Tpcn1/2(-/-) tissue, suggesting that NAADP regulation is conferred by an accessory protein. Altogether, our data establish TPCs as Ca(2+)-permeable channels indispensable for NAADP signalling.
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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.