ArticleeLife2020
Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function.
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Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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97citing papers in PubMed
14.3field-weighted citation impact, top 1% of its field
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Who cites it
97 citing papers in PubMed, 151 citations in OpenAlex.
- 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
- TPC1-dependent control of endosomal pH and transferrin uptake determines cellular iron status.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Endosomal TPC1-mediated CaProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Two-pore channel-2 controls calmodulin-dependent STIM1 inactivation.Nature communications · 2026Article
- The lysosomal cation channel TRPML1 regulates the oligodendrocyte cytoskeleton.bioRxiv : the preprint server for biology · 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
- Review
- TRPML1 suppresses pulmonary fibrosis by limiting collagen and elastin deposition.The EMBO journal · 2026Article
- Activation of TPC2 amplifies lysosome-mitochondria calcium transfer to regulate energetic stress responses.bioRxiv : the preprint server for biology · 2026Article
- Review
- Liquid liquid phase separation of the intrinsically disordered protein JPT2 compartmentalizes components of NAADP-evoked CabioRxiv : the preprint server for biology · 2026Article
- Tetrandrine-driven autophagy suppresses SARS-CoV-2 replication by modulating cholesterol and IGF signaling pathways.Cell death discovery · 2026Article
- Lysosomal exocytosis by macrophages as a druggable mechanism for anti-inflammatory clearance of dead adipocytes in adipose tissue.Cell death & disease · 2025Article
- The Two-Pore Channel 2 in Human Physiology and Diseases: Functional Characterisation and Pharmacology.International journal of molecular sciences · 2025Review
- Lysosomal ion channels and pain.Pain reports · 2025Review
- Tetrandrine regulates NAADP-mediated calcium signaling through a LIMP-2-dependent and sphingosine-mediated mechanism.Nature communications · 2025Article
- Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson's disease.The Journal of cell biology · 2025Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 4 countries.
Susanne Gerndt *Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität, Munich, Germany.
Cheng-Chang Chen *Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität, Munich, Germany.ORCID 0000-0003-1282-4026
Yu-Kai Chao *Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.ORCID 0000-0002-1202-2448
Yu Yuan *Department of Cell and Developmental Biology, University College London, London, United Kingdom.
Sandra BurgstallerMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria.
Anna Scotto RosatoWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
Einar KrogsaeterWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.ORCID 0000-0001-8232-5498
Nicole UrbanRudolf-Boehm-Institute for Pharmacology and Toxicology, Universität Leipzig, Leipzig, Germany.
Katharina JacobWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
Ong Nam Phuong NguyenDepartment of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität, Munich, Germany.
Meghan T MillerDepartment of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität, Munich, Germany.
Marco KellerDepartment of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität, Munich, Germany.
Angelika M VollmarDepartment of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität, Munich, Germany.
Thomas GudermannWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.
Susanna ZierlerWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.ORCID 0000-0002-4684-0385
Johann SchredelsekerDepartment of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität, Munich, Germany.ORCID 0000-0002-6657-0466
Michael SchaeferDepartment of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität, Munich, Germany.
Martin BielDepartment of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität, Munich, Germany.
Roland MalliMolecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria.ORCID 0000-0001-6327-8729
Christian Wahl-SchottInstitute for Neurophysiology, Hannover Medical School, Hannover, Germany.
Franz BracherDepartment of Pharmacy - Center for Drug Research, Ludwig-Maximilians-Universität, Munich, Germany.
Sandip PatelDepartment of Cell and Developmental Biology, University College London, London, United Kingdom.
Christian GrimmWalther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-Universität, Munich, Germany.ORCID 0000-0002-0177-5559
Ludwig-Maximilians-Universität München · DEMedical University of Graz · ATUniversity College London · GBLeipzig University · DEMedizinische Hochschule Hannover · DERoche (Switzerland) · CH
Funding
Biotechnology and Biological Sciences Research Council BB/N01524X/1Deutsche Forschungsgemeinschaft 239283807Deutsche Forschungsgemeinschaft BR 1034/7-1Deutsche Forschungsgemeinschaft GR 4315/2-1Deutsche Forschungsgemeinschaft SFB/TRR152 P04Deutsche Forschungsgemeinschaft SFB/TRR152 P06Deutsche Forschungsgemeinschaft SFB/TRR152 P12Deutsche Forschungsgemeinschaft SFB/TRR152 P14Mucolipidosis IV Foundation 404.510.2577Mucolipidosis IV Foundation MDBR-17-120- ML4NCL Foundation 2018-Grimm-PaquetParkinson's UK H-1202
Abstract
Ion selectivity is a defining feature of a given ion channel and is considered immutable. Here we show that ion selectivity of the lysosomal ion channel TPC2, which is hotly debated (Calcraft et al., 2009; Guo et al., 2017; Jha et al., 2014; Ruas et al., 2015; Wang et al., 2012), depends on the activating ligand. A high-throughput screen identified two structurally distinct TPC2 agonists. One of these evoked robust Ca
Indexed as
AnimalsBenzylisoquinolinesCalciumCalcium Channel AgonistsCalcium ChannelsFluphenazineGene Expression RegulationHEK293 CellsHeLa CellsHumansIonomycinMacrophagesMiceNADPPhosphatidylinositol PhosphatesRaloxifene HydrochlorideBenzylisoquinolinesCalciumCalcium Channel AgonistsCalcium ChannelsFluphenazineIonomycinNAADPNADPphosphatidylinositol 3,5-diphosphatePhosphatidylinositol PhosphatesRaloxifene HydrochlorideSodiumtetrandrineTPCN2 protein, humanTPCN2 protein, mousebiochemistrychemical biologyhumanlysosomemouseNAADPPI(3,5)P2TPCTPC2two-pore channel 2
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