ArticleScience signaling2014
Two-pore channels provide insight into the evolution of voltage-gated Ca2+ and Na+ channels.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 109 citations in OpenAlex.
- Allosteric switching of CaThe EMBO journal · 2026Article
- Review
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Review
- Liquid liquid phase separation of the intrinsically disordered protein JPT2 compartmentalizes components of NAADP-evoked CabioRxiv : the preprint server for biology · 2026Article
- The Two-Pore Channel 2 in Human Physiology and Diseases: Functional Characterisation and Pharmacology.International journal of molecular sciences · 2025Review
- Inter-Organellar CaCells · 2025Review
- Lysosomal TPC2 channels disrupt Ca2+ entry and dopaminergic function in models of LRRK2-Parkinson's disease.The Journal of cell biology · 2025Article
- In silico characterization of the gating and selectivity mechanism of the human TPC2 cation channel.The Journal of general physiology · 2025Article
- The chemistry of electrical signaling in sodium channels from bacteria and beyond.Cell chemical biology · 2024Review
- 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
- Convergent activation of CaScience signaling · 2023Article
- NAADP-Mediated CaHandbook of experimental pharmacology · 2023Article
- Endo-Lysosomal Two-Pore Channels and Their Protein Partners.Handbook of experimental pharmacology · 2023Review
- Structure and Function of Plant and Mammalian TPC Channels.Handbook of experimental pharmacology · 2023Article
- TPC1-Type Channels inPlants (Basel, Switzerland) · 2022Article
- Two-pore channels: going with the flows.Biochemical Society transactions · 2022Article
- Review
- Segregated cation flux by TPC2 biases CaNature communications · 2022Article
- Two-pore channel blockade by phosphoinositide kinase inhibitors YM201636 and PI-103 determined by a histidine residue near pore-entrance.Communications biology · 2022Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Four-domain voltage-gated Ca(2+) and Na(+) channels (CaV, NaV) underpin nervous system function and likely emerged upon intragenic duplication of a primordial two-domain precursor. To investigate if two-pore channels (TPCs) may represent an intermediate in this evolutionary transition, we performed molecular docking simulations with a homology model of TPC1, which suggested that the pore region could bind antagonists of CaV or NaV. CaV or NaV antagonists blocked NAADP (nicotinic acid adenine dinucleotide phosphate)-evoked Ca(2+) signals in sea urchin egg preparations and in intact cells that overexpressed TPC1. By sequence analysis and inspection of the model, we predicted a noncanonical selectivity filter in animal TPCs in which the carbonyl groups of conserved asparagine residues are positioned to coordinate cations. In contrast, a distinct clade of TPCs [TPCR (for TPC-related)] in several unicellular species had ion selectivity filters with acidic residues more akin to CaV. TPCRs were predicted to interact strongly with CaV antagonists. Our data suggest that acquisition of a "blueprint" pharmacological profile and changes in ion selectivity within four-domain voltage-gated ion channels may have predated intragenic duplication of an ancient two-domain ancestor.
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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.