ArticleeLife2019
A FRET sensor of C-terminal movement reveals VRAC activation by plasma membrane DAG signaling rather than ionic strength.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Structures of the volume-regulated anion channel LRRC8A/D in activating and inhibiting conditions.Nature communications · 2026Article
- The intracellular subdomain of the volume-regulated anion channel subunit LRRC8A is a hotspot of channel activation.Nature communications · 2026Article
- Puromycin-sensitive aminopeptidase acts as an inhibitory auxiliary subunit of volume-regulated anion channels and regulates cGAMP transport.Molecular cell · 2025Article
- A conserved mechanism of LRRC8 channel inhibition by two structurally distinct drugs.Communications biology · 2025Article
- Sphingosine-1-phosphate activates LRRC8 volume-regulated anion channels through Gβγ signalling.The Journal of physiology · 2025Article
- Recent advances in the structure, function and regulation of the volume-regulated anion channels and their role in immunity.The Journal of physiology · 2025Review
- The Volume-Regulated Anion Channel LRRC8 is Involved in the Initiation of Epidermal Differentiation and is Deregulated in Psoriasis.JID innovations : skin science from molecules to population health · 2025Article
- Endothelial tip-cell position, filopodia formation and biomechanics require BMPR2 expression and signaling.Communications biology · 2025Article
- Interactomic exploration of LRRC8A in volume-regulated anion channels.Cell death discovery · 2024Article
- Physiology of the volume-sensitive/regulatory anion channel VSOR/VRAC: part 2: its activation mechanisms and essential roles in organic signal release.The journal of physiological sciences : JPS · 2024Review
- Comprehensive review on the novel immunotherapy target: Leucine-rich repeat-containing 8A/volume-regulated anion channel.International journal of biological sciences · 2024Review
- Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.Handbook of experimental pharmacology · 2024Article
- Structural insights into anion selectivity and activation mechanism of LRRC8 volume-regulated anion channels.Cell reports · 2023Article
- Review
- Structural basis for assembly and lipid-mediated gating of LRRC8A:C volume-regulated anion channels.Nature structural & molecular biology · 2023Article
- Cryo-EM structures of an LRRC8 chimera with native functional properties reveal heptameric assembly.eLife · 2023Article
- Structure of a volume-regulated heteromeric LRRC8A/C channel.Nature structural & molecular biology · 2023Article
- Trends in volume-regulated anion channel (VRAC) research: visualization and bibliometric analysis from 2014 to 2022.Frontiers in pharmacology · 2023Article
- Identification of the chloride channel, leucine-rich repeat-containing protein 8, subfamily a (LRRC8A), in mouse cholangiocytes.Hepatology (Baltimore, Md.) · 2022Article
- Molecular determinants underlying volume-regulated anion channel subunit-dependent oxidation sensitivity.The Journal of physiology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Volume-regulated anion channels (VRACs) are central to cell volume regulation. Recently identified as hetero-hexamers formed by LRRC8 proteins, their activation mechanism remains elusive. Here, we measured Förster resonance energy transfer (FRET) between fluorescent proteins fused to the C-termini of LRRC8 subunits. Inter-subunit FRET from LRRC8 complexes tracked VRAC activation. With patch-clamp fluorometry, we confirmed that the cytoplasmic domains rearrange during VRAC opening. With these FRET reporters, we determined VRAC activation, non-invasively, in live cells and their subcompartments. Reduced intracellular ionic strength did not directly activate VRACs, and VRACs were not activated on endomembranes. Instead, pharmacological manipulation of diacylglycerol (DAG), and protein kinase D (PKD) activity, activated or inhibited plasma membrane-localized VRACs. Finally, we resolved previous contradictory reports concerning VRAC activation, using FRET to detect robust activation by PMA that was absent during whole-cell patch clamp. Overall, non-invasive VRAC measurement by FRET is an essential tool for unraveling its activation mechanism.
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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.