ArticleNature communications2021
Allosteric modulation of LRRC8 channels by targeting their cytoplasmic domains.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 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
- Article
- Cross-species dissection of saline-related genes by genetically deciphering a euryhaline microalga Chlorella sp.Nature communications · 2026Article
- Strategic advances for cryo-EM structural studies of small (<100 kDa) GPCRs.Communications biology · 2026Review
- Structural biology of the TRPM4 channel: architecture, modulation, and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- Puromycin-sensitive aminopeptidase acts as an inhibitory auxiliary subunit of volume-regulated anion channels and regulates cGAMP transport.Molecular cell · 2025Article
- NAA60 facilitates LRRC8A- and LRRC8D-mediated platinum drug uptake.Communications biology · 2025Article
- A conserved mechanism of LRRC8 channel inhibition by two structurally distinct drugs.Communications biology · 2025Article
- Puromycin-sensitive aminopeptidase acts as an inhibitory auxiliary subunit of volume-regulated anion channels.bioRxiv : the preprint server for biology · 2025Article
- Article
- Sphingosine-1-phosphate activates LRRC8 volume-regulated anion channels through Gβγ signalling.The Journal of physiology · 2025Article
- 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
- Rigid enlargement of sybodies with antibody fragments for cryo-EM analyses of small membrane proteins.Scientific reports · 2025Article
- Regulation of volume-regulated anion channels alters sensitivity to platinum chemotherapy.Science advances · 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
- Physiological Functions of the Volume-Regulated Anion Channel VRAC/LRRC8 and the Proton-Activated Chloride Channel ASOR/TMEM206.Handbook of experimental pharmacology · 2024Article
- Comprehensive review on the novel immunotherapy target: Leucine-rich repeat-containing 8A/volume-regulated anion channel.International journal of biological sciences · 2024Review
- Structural insights into anion selectivity and activation mechanism of LRRC8 volume-regulated anion channels.Cell reports · 2023Article
- Structural basis for assembly and lipid-mediated gating of LRRC8A:C volume-regulated anion channels.Nature structural & molecular biology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Members of the LRRC8 family form heteromeric assemblies, which function as volume-regulated anion channels. These modular proteins consist of a transmembrane pore and cytoplasmic leucine-rich repeat (LRR) domains. Despite their known molecular architecture, the mechanism of activation and the role of the LRR domains in this process has remained elusive. Here we address this question by generating synthetic nanobodies, termed sybodies, which target the LRR domain of the obligatory subunit LRRC8A. We use these binders to investigate their interaction with homomeric LRRC8A channels by cryo-electron microscopy and the consequent effect on channel activation by electrophysiology. The five identified sybodies either inhibit or enhance activity by binding to distinct epitopes of the LRR domain, thereby altering channel conformations. In combination, our work provides a set of specific modulators of LRRC8 proteins and reveals the role of their cytoplasmic domains as regulators of channel activity by allosteric mechanisms.
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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.