ArticleThe Journal of biological chemistry2012
Membrane potential regulates nicotinic acid adenine dinucleotide phosphate (NAADP) dependence of the pH- and Ca2+-sensitive organellar two-pore channel TPC1.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- The protein interaction networks of mucolipins and two-pore channels.Biochimica et biophysica acta. Molecular cell research · 2019Pooled it
- NAADP-Dependent TPC Current.Handbook of experimental pharmacology · 2023Article
- Structure and Function of Plant and Mammalian TPC Channels.Handbook of experimental pharmacology · 2023Article
- Two-pore channels: going with the flows.Biochemical Society transactions · 2022Article
- Review
- Activation of endo-lysosomal two-pore channels by NAADP and PI(3,5)PCell calcium · 2022Review
- Current Methods to Unravel the Functional Properties of Lysosomal Ion Channels and Transporters.Cells · 2022Review
- NAADP-binding proteins find their identity.Trends in biochemical sciences · 2022Review
- Review
- NAADP-induced intracellular calcium ion is mediated by the TPCs (two-pore channels) in hypoxia-induced pulmonary arterial hypertension.Journal of cellular and molecular medicine · 2021Article
- Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function.eLife · 2020Article
- Role of Two-Pore Channels in Embryonic Development and Cellular Differentiation.Cold Spring Harbor perspectives in biology · 2020Review
- Endolysosomal CaCancers · 2018Review
- mTORC1 controls lysosomal CaScience signaling · 2018Article
- Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel.Nature · 2018Article
- Two-pore channels open up.Nature · 2018Article
- On the structure and mechanism of two-pore channels.The FEBS journal · 2018Article
- The human two-pore channel 1 is modulated by cytosolic and luminal calcium.Scientific reports · 2017Article
- Activity-Dependent Exocytosis of Lysosomes Regulates the Structural Plasticity of Dendritic Spines.Neuron · 2017Article
- Two-pore channels (TPCs): Novel voltage-gated ion channels with pleiotropic functions.Channels (Austin, Tex.) · 2017Review
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent second messenger that mobilizes Ca(2+) from the acidic endolysosomes by activation of the two-pore channels TPC1 and TPC2. The channel properties of human TPC1 have not been studied before, and its cellular function is not known. In the present study, we characterized TPC1 incorporated into lipid bilayers. The native and recombinant TPC1 channels are activated by NAADP. TPC1 activity requires acidic luminal pH and high luminal Ca(2+). With Ba(2+) as the permeable ion, luminal Ca(2+) activates TPC1 with an apparent K(m) of 180 μm. TPC1 operates in two tightly coupled conductance states of 47 ± 8 and 200 ± 9 picosiemens. Importantly, opening of the large conductance markedly increases the small conductance mean open time. Changes in membrane potential from 0 to -60 mV increased linearly both the small and the large conductances and NP(o), indicating that TPC1 is regulated by voltage. Intriguingly, the apparent affinity for activation of TPC1 by its ligand NAADP is not constant. Rather, hyperpolarization increases the apparent affinity of TPC1 for NAADP by 10 nm/mV. The concerted regulation of TPC1 activity by luminal Ca(2+) and by membrane potential thus provides a potential mechanism to explain NAADP-induced Ca(2+) oscillations. These findings reveal unique properties of TPC1 to explain its role in Ca(2+) oscillations and cell function.
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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.