ArticlePflugers Archiv : European journal of physiology2009
The two-pore channel TPCN2 mediates NAADP-dependent Ca(2+)-release from lysosomal stores.
Article in Pflugers Archiv : European journal of physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 180 papers.
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Who cites it
180 citing papers in PubMed, 270 citations in OpenAlex.
- Allosteric switching of CaThe EMBO journal · 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
- Review
- Liquid liquid phase separation of the intrinsically disordered protein JPT2 compartmentalizes components of NAADP-evoked CabioRxiv : the preprint server for biology · 2026Article
- Calcium signalling and organelle crosstalk in cardiovascular disease: an interplay of cardiac cell death pathways.Molecular biology reports · 2025Review
- Lysosome and plasma membrane Piezo channels of Trypanosoma cruzi are essential for proliferation, differentiation and infectivity.PLoS pathogens · 2025Article
- Circadian Regulation of Vitamin D Target Genes Reveals a Network Shaped by Individual Responsiveness.Nutrients · 2025Article
- Two-pore channel 2 is required for soluble adenylyl cyclase-dependent regulation of melanosomal pH and melanin synthesis.Pigment cell & melanoma research · 2024Article
- Plasticity of the selectivity filter is essential for permeation in lysosomal TPC2 channels.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The ion channels of endomembranes.Physiological reviews · 2024Review
- Two-pore channel regulators - Who is in control?Frontiers in physiology · 2024Review
- Convergent activation of CaScience signaling · 2023Article
- NAADP-Evoked CaInternational journal of molecular sciences · 2023Article
- Endolysosomal TPCs regulate social behavior by controlling oxytocin secretion.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Conformational rearrangements in the second voltage sensor domain switch PIPProceedings of the National Academy of Sciences of the United States of America · 2023Article
- A gain-of-function TPC2 variant R210C increases affinity to PI(3,5)PNature communications · 2023Article
- NAADP-Evoked CaHandbook of experimental pharmacology · 2023Article
- Characterization of Endo-Lysosomal Cation Channels Using Calcium Imaging.Handbook of experimental pharmacology · 2023Article
- TPC Functions in the Immune System.Handbook of experimental pharmacology · 2023Article
120 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Second messenger-induced Ca(2+)-release from intracellular stores plays a key role in a multitude of physiological processes. In addition to 1,4,5-inositol trisphosphate (IP(3)), Ca(2+), and cyclic ADP ribose (cADPR) that trigger Ca(2+)-release from the endoplasmatic reticulum (ER), nicotinic acid adenine dinucleotide phosphate (NAADP) has been identified as a cellular metabolite that mediates Ca(2+)-release from lysosomal stores. While NAADP-induced Ca(2+)-release has been found in many tissues and cell types, the molecular identity of the channel(s) conferring this release remained elusive so far. Here, we show that TPCN2, a novel member of the two-pore cation channel family, displays the basic properties of native NAADP-dependent Ca(2+)-release channels. TPCN2 transcripts are widely expressed in the body and encode a lysosomal protein forming homomers. TPCN2 mediates intracellular Ca(2+)-release after activation with low-nanomolar concentrations of NAADP while it is desensitized by micromolar concentrations of this second messenger and is insensitive to the NAADP analog nicotinamide adenine dinucleotide phosphate (NADP). Furthermore, TPCN2-mediated Ca(2+)-release is almost completely abolished when the capacity of lysosomes for storing Ca(2+) is pharmacologically blocked. By contrast, TPCN2-specific Ca(2+)-release is unaffected by emptying ER-based Ca(2+) stores. In conclusion, these findings indicate that TPCN2 is a major component of the long-sought lysosomal NAADP-dependent Ca(2+)-release channel.
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