ArticleCurrent biology : CB2010
Purified TPC isoforms form NAADP receptors with distinct roles for Ca(2+) signaling and endolysosomal trafficking.
Article in Current biology : CB, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 1 of them a synthesis that pooled it.
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Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Stay in touch with the endoplasmic reticulum.Science China. Life sciences · 2024Pooled it
- Endolysosomal two-pore channels regulate a conserved entry pathway for enteroviruses.The Journal of general virology · 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
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Cepharanthine inhibits enterovirus entry by endolysosomal deacidification and exhibits protective activityAntimicrobial agents and chemotherapy · 2025Article
- Lysosomal TMEM165 controls cellular ion homeostasis and survival by mediating lysosomal CaNature communications · 2025Article
- Review
- Endoplasmic Reticulum Calcium Signaling in Hippocampal Neurons.Biomolecules · 2024Review
- Rab7a is an enhancer of TPC2 activity regulating melanoma progression through modulation of the GSK3β/β-Catenin/MITF-axis.Nature communications · 2024Article
- Two-pore channel 2 is required for soluble adenylyl cyclase-dependent regulation of melanosomal pH and melanin synthesis.Pigment cell & melanoma research · 2024Article
- The ion channels of endomembranes.Physiological reviews · 2024Review
- Endolysosomal transient receptor potential mucolipins and two-pore channels: implications for cancer immunity.Frontiers in immunology · 2024Review
- Review
- NAADP-Dependent TPC Current.Handbook of experimental pharmacology · 2023Article
- NAADP-Mediated CaHandbook of experimental pharmacology · 2023Article
- Endo-Lysosomal Two-Pore Channels and Their Protein Partners.Handbook of experimental pharmacology · 2023Review
- Lysosomal solute and water transport.The Journal of cell biology · 2022Review
- TPC2 rescues lysosomal storage in mucolipidosis type IV, Niemann-Pick type C1, and Batten disease.EMBO molecular medicine · 2022Article
- Two-pore channels: going with the flows.Biochemical Society transactions · 2022Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Intracellular Ca(2+) signals constitute key elements in signal transduction. Of the three major Ca(2+) mobilizing messengers described, the most potent, nicotinic acid adenine dinucleotide phosphate (NAADP) is the least well understood in terms of its molecular targets [1]. Recently, we showed that heterologous expression of two-pore channel (TPC) proteins enhances NAADP-induced Ca(2+) release, whereas the NAADP response was abolished in pancreatic beta cells from Tpcn2 gene knockout mice [2]. However, whether TPCs constitute native NAADP receptors is unclear. Here we show that immunopurified endogenous TPC complexes possess the hallmark properties ascribed to NAADP receptors, including nanomolar ligand affinity [3-5]. Our study also reveals important functional differences between the three TPC isoforms. Thus, TPC1 and TPC2 both mediate NAADP-induced Ca(2+) release, but the subsequent amplification of this trigger Ca(2+) by IP(3)Rs is more tightly coupled for TPC2. In contrast, TPC3 expression suppressed NAADP-induced Ca(2+) release. Finally, increased TPC expression has dramatic and contrasting effects on endolysosomal structures and dynamics, implicating a role for NAADP in the regulation of vesicular trafficking. We propose that NAADP regulates endolysosomal Ca(2+) storage and release via TPCs and coordinates endoplasmic reticulum Ca(2+) release in a role that impacts on Ca(2+) signaling in health and disease [6].
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