ArticlePhysiological reports2016
Leucine-rich repeat containing protein LRRC8A is essential for swelling-activated Cl- currents and embryonic development in zebrafish.
Article in Physiological reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Recent advances in the structure, function and regulation of the volume-regulated anion channels and their role in immunity.The Journal of physiology · 2025Review
- Disruption of Swell1/VRAC function impairs initial hemodynamics and activates compensatory leukotriene signaling in zebrafish circulation development.Frontiers in cell and developmental biology · 2025Article
- 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
- Cryo-EM structures of an LRRC8 chimera with native functional properties reveal heptameric assembly.eLife · 2023Article
- Study on the Association betweenGenes · 2023Article
- LRRC8A homohexameric channels poorly recapitulate VRAC regulation and pharmacology.American journal of physiology. Cell physiology · 2021Article
- LRRC8 family proteins within lysosomes regulate cellular osmoregulation and enhance cell survival to multiple physiological stresses.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Leucine-rich repeat containing 8A contributes to the expansion of brain ventricles in zebrafish embryos.Biology open · 2020Article
- Cell Death Induction and Protection by Activation of Ubiquitously Expressed Anion/Cation Channels. Part 1: Roles of VSOR/VRAC in Cell Volume Regulation, Release of Double-Edged Signals and Apoptotic/Necrotic Cell Death.Frontiers in cell and developmental biology · 2020Review
- Absolute Protein Amounts and Relative Abundance of Volume-regulated Anion Channel (VRAC) LRRC8 Subunits in Cells and Tissues Revealed by Quantitative Immunoblotting.International journal of molecular sciences · 2019Article
- Biophysics and Structure-Function Relationships of LRRC8-Formed Volume-Regulated Anion Channels.Biophysical journal · 2019Review
- Review
- A 30-year journey from volume-regulated anion currents to molecular structure of the LRRC8 channel.The Journal of general physiology · 2019Review
- High expression of leucine‑rich repeat‑containing 8A is indicative of a worse outcome of colon cancer patients by enhancing cancer cell growth and metastasis.Oncology reports · 2018Article
- Intracellular and extracellular loops of LRRC8 are essential for volume-regulated anion channel function.The Journal of general physiology · 2018Article
- In vivo monitoring of intracellular CaIslets · 2018Article
- Molecular Biology and Physiology of Volume-Regulated Anion Channel (VRAC).Current topics in membranes · 2018Review
- Leucine-rich repeat containing protein LRRC8A is essential for swelling-activated Cl- currents and embryonic development in zebrafish.Physiological reports · 2016Article
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
A volume-regulated anion channel (VRAC) has been electrophysiologically characterized in innumerable mammalian cell types. VRAC is activated by cell swelling and mediates the volume regulatory efflux of Cl(-) and small organic solutes from cells. Two groups recently identified the mammalian leucine-rich repeat containing protein LRRC8A as an essential VRAC component. LRRC8A must be coexpressed with at least one of the other four members of this gene family, LRRC8B-E, to reconstitute VRAC activity in LRRC8(-/-) cells. LRRC8 genes likely arose with the origin of chordates. We identified LRRC8A and LRRC8C-E orthologs in the zebrafish genome and demonstrate that zebrafish embryo cells and differentiated adult cell types express a swelling-activated Cl(-) current indistinguishable from mammalian VRAC currents. Embryo cell VRAC currents are virtually eliminated by morpholino knockdown of the zebrafish LRRC8A ortholog lrrc8aa VRAC activity is fully reconstituted in LRRC8(-/-) human cells by coexpression of zebrafish lrrc8aa and human LRRC8C cDNAs. lrrc8aa expression varies during zebrafish embryogenesis and lrrc8aa knockdown causes pericardial edema and defects in trunk elongation and somatogenesis. Our studies provide confirmation of the importance of LRRC8A in VRAC activity and establish the zebrafish as a model system for characterizing the molecular regulation and physiological roles of VRAC and LRRC8 proteins.
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