ArticleThe Journal of biological chemistry2011
Membrane topology of NAADP-sensitive two-pore channels and their regulation by N-linked glycosylation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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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
40 citing papers in PubMed, 59 citations in OpenAlex.
- O-linked glycan-dependent gating of TPC2 controls lysosomal excitability and organelle remodeling.Nature communications · 2026Article
- Hypoxia-induced TPC2 transcription and glycosylation aggravates pulmonary arterial hypertension by blocking autophagy flux.Scientific reports · 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
- TPC Functions in the Immune System.Handbook of experimental pharmacology · 2023Article
- Endo-Lysosomal Two-Pore Channels and Their Protein Partners.Handbook of experimental pharmacology · 2023Review
- Two-Pore Channels Regulate Inter-Organellar CaCells · 2022Review
- Genetic and biochemical characterizations of Zika virus NS2A protein.Emerging microbes & infections · 2019Article
- Endolysosomal CaCancers · 2018Review
- Two-pore channels and disease.Biochimica et biophysica acta. Molecular cell research · 2018Review
- Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel.Nature · 2018Article
- On the structure and mechanism of two-pore channels.The FEBS journal · 2018Article
- NAADP-evoked CaCell calcium · 2017Article
- The two-pore channel TPC1 is required for efficient protein processing through early and recycling endosomes.Scientific reports · 2017Article
- Two-pore channels (TPCs): Novel voltage-gated ion channels with pleiotropic functions.Channels (Austin, Tex.) · 2017Review
- Isolated pores dissected from human two-pore channel 2 are functional.Scientific reports · 2016Article
- Exploring the biophysical evidence that mammalian two-pore channels are NAADP-activated calcium-permeable channels.The Journal of physiology · 2016Review
- Ca2+/H+ exchange by acidic organelles regulates cell migration in vivo.The Journal of cell biology · 2016Article
- Two-Pore Channels: Lessons from Mutant Mouse Models.Messenger (Los Angeles, Calif. : Print) · 2015Article
- Two-pore channels at the intersection of endolysosomal membrane traffic.Biochemical Society transactions · 2015Review
- Poring over two-pore channel pore mutants.Messenger (Los Angeles, Calif. : Print) · 2015Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Two-pore channels (TPCs) localize to the endolysosomal system and have recently emerged as targets for the Ca(2+)-mobilizing messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). However, their membrane topology is unknown. Using fluorescence protease protection assays, we show that human TPC1 and TPC2 possess cytosolic N and C termini and therefore an even number of transmembrane regions. Fluorophores placed at position 225 or 347 in TPC1, or 339 in TPC2 were also cytosolic, whereas a fluorophore at position 628 in TPC1 was luminal. These data together with sequence similarity to voltage-gated Ca(2+) and Na(+) channels, and unbiased in silico predictions are consistent with a topology in which two homologous domains are present, each comprising 6 transmembrane regions and a re-entrant pore loop. Immunocytochemical analysis of selectively permeabilized cells using antipeptide antibodies confirmed that the C-terminal tails of recombinant TPCs are cytosolic and that residues 240-254 of TPC2 prior to putative pore 1 are luminal. Both TPC1 and TPC2 are N-glycosylated with residues 599, 611, and 616 contributing to glycosylation of TPC1. This confirms the luminal position of these residues, which immediately precede the putative pore loop of the second domain. Mutation of all three glycosylation sites in TPC1 enhances NAADP-evoked cytosolic Ca(2+) signals. Our data establish essential features of the topology of two-pore channels.
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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.