ArticleScience signaling2009
TRPM2 functions as a lysosomal Ca2+-release channel in beta cells.
Article in Science signaling, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 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
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 295 citations in OpenAlex.
- Pooled it
- Emerging chemical strategies for CD38 inhibition: restoring NADBioorganic & medicinal chemistry · 2026Review
- Article
- Just a little prick: careful cell contacts enabled by ceramic nanostraws.Pflugers Archiv : European journal of physiology · 2026Article
- Inter-Organellar CaCells · 2025Review
- The Link Between Endoplasmic Reticulum Stress and Lysosomal Dysfunction Under Oxidative Stress in Cancer Cells.Biomolecules · 2025Review
- TRPM2 channels mediate ROS-induced actin remodeling and cell migration of prostate cancer cells.BMC cancer · 2025Article
- Targeting the Galectin-7/TRPM2/ZnAllergy · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- Autophagy-lysosome pathway in insulin & glucagon homeostasis.Frontiers in endocrinology · 2025Review
- The impact of sulfonylureas on diverse ion channels: an alternative explanation for the antidiabetic actions.Frontiers in cell and developmental biology · 2025Review
- Article
- TRP Channels in Stroke.Neuroscience bulletin · 2024Review
- ER-to-lysosome CaeLife · 2024Article
- The ion channels of endomembranes.Physiological reviews · 2024Review
- 2'-deoxy-ADPR activates human TRPM2 faster than ADPR and thereby induces higher currents at physiological CaFrontiers in immunology · 2024Article
- CD38/ADP-ribose/TRPM2-mediated nuclear CaExperimental & molecular medicine · 2023Article
- TRPM2 Channels: A Potential Therapeutic Target in Melanoma?International journal of molecular sciences · 2023Review
- TRPM2-mediated CaCell communication and signaling : CCS · 2023Review
- TPC Functions in the Immune System.Handbook of experimental pharmacology · 2023Article
86 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 at 3 institutions in 2 countries.
Funding
Abstract
TRPM2 is a Ca2+-permeable cation channel that is specifically activated by adenosine diphosphoribose (ADPR). Channel activation in the plasma membrane leads to Ca2+ influx and has been linked to apoptotic mechanisms. The primary agonist, ADPR, is produced both extra- and intracellularly and causes increases in intracellular calcium concentration ([Ca2+]i), but the mechanisms involved are not understood. Using short interfering RNA and a knockout mouse, we report that TRPM2, in addition to its role as a plasma membrane channel, also functions as a Ca2+-release channel activated by intracellular ADPR in a lysosomal compartment. We show that both functions of TRPM2 are critically linked to hydrogen peroxide-induced beta cell death. Additionally, extracellular ADPR production by the ectoenzyme CD38 from its substrates NAD+ (nicotinamide adenine dinucleotide) or cADPR causes IP3-dependent Ca2+ release via P2Y and adenosine receptors. Thus, ADPR and TRPM2 represent multimodal signaling elements regulating Ca2+ mobilization in beta cells through membrane depolarization, Ca2+ influx, and release of Ca2+ from intracellular stores.
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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.