ArticleThe Journal of biological chemistry2016
Inactivation and Anion Selectivity of Volume-regulated Anion Channels (VRACs) Depend on C-terminal Residues of the First Extracellular Loop.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 65 citations in OpenAlex.
- Structures of the volume-regulated anion channel LRRC8A/D in activating and inhibiting conditions.Nature communications · 2026Article
- VRAC coordinates the trade-off between nutrient absorption and antimicrobial defense in enterocytes against inflammation.Nature communications · 2026Article
- A conserved mechanism of LRRC8 channel inhibition by two structurally distinct drugs.Communications biology · 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
- Physiology of the volume-sensitive/regulatory anion channel VSOR/VRAC. Part 1: from its discovery and phenotype characterization to the molecular entity identification.The journal of physiological sciences : JPS · 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
- ATP modulation of osmotically activated anionic current in the membrane of Phycomyces blakesleeanus sporangiophore.Scientific reports · 2023Article
- 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
- Trends in volume-regulated anion channel (VRAC) research: visualization and bibliometric analysis from 2014 to 2022.Frontiers in pharmacology · 2023Article
- Structure of a volume-regulated heteromeric LRRC8A/C channel.Nature structural & molecular biology · 2023Article
- Ion Channel Involvement in Tumor Drug Resistance.Journal of personalized medicine · 2022Review
- Structure-function relationships of the LRRC8 subunits and subdomains of the volume-regulated anion channel (VRAC).Frontiers in cellular neuroscience · 2022Review
- Recent Advances in the Structural Biology of the Volume-Regulated Anion Channel LRRC8.Frontiers in pharmacology · 2022Review
- Late adolescence mortality in mice with brain-specific deletion of the volume-regulated anion channel subunit LRRC8A.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Allosteric modulation of LRRC8 channels by targeting their cytoplasmic domains.Nature communications · 2021Article
- LRRC8A homohexameric channels poorly recapitulate VRAC regulation and pharmacology.American journal of physiology. Cell physiology · 2021Article
- Properties, Structures, and Physiological Roles of Three Types of Anion Channels Molecularly Identified in the 2010's.Frontiers in physiology · 2021Review
- Flow fluorometry quantification of anion channel VRAC subunit LRRC8A at the membrane of living U937 cells.Channels (Austin, Tex.) · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Canonical volume-regulated anion channels (VRACs) are crucial for cell volume regulation and have many other important roles, including tumor drug resistance and release of neurotransmitters. Although VRAC-mediated swelling-activated chloride currents (ICl,vol) have been studied for decades, exploration of the structure-function relationship of VRAC has become possible only after the recent discovery that VRACs are formed by differently composed heteromers of LRRC8 proteins. Inactivation of ICl,vol at positive potentials, a typical hallmark of VRACs, strongly varies between native cell types. Exploiting the large differences in inactivation between different LRRC8 heteromers, we now used chimeras assembled from isoforms LRRC8C and LRRC8E to uncover a highly conserved extracellular region preceding the second LRRC8 transmembrane domain as a major determinant of ICl,vol inactivation. Point mutations identified two amino acids (Lys-98 and Asp-100 in LRRC8A and equivalent residues in LRRC8C and -E), which upon charge reversal strongly altered the kinetics and voltage dependence of inactivation. Importantly, charge reversal at the first position also reduced the iodide > chloride permeability of ICl,vol This change in selectivity was stronger when both the obligatory LRRC8A subunit and the other co-expressed isoform (LRR8C or -E) carried such mutations. Hence, the C-terminal part of the first extracellular loop not only determines VRAC inactivation but might also participate in forming its outer pore. Inactivation of VRACs may involve a closure of the extracellular mouth of the permeation pathway.
Indexed as
Identifiers
What OpenQuestion holds
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.