Ask about this productRelated genes to: LRRC8B antibody
- Gene:
- LRRC8B NIH gene
- Name:
- leucine rich repeat containing 8 VRAC subunit B
- Previous symbol:
- -
- Synonyms:
- TA-LRRP, KIAA0231
- Chromosome:
- 1p22.2
- Locus Type:
- gene with protein product
- Date approved:
- 2005-06-29
- Date modifiied:
- 2018-05-08
Related products to: LRRC8B antibody
Related articles to: LRRC8B antibody
- Endothelial mechanosensing is essential for controlling vascular tone. LRRC8A (leucine-rich repeat-containing protein 8A) was previously identified as a core subunit of the mechanoresponsive LRRC8 complex, functionally encoding the endothelial volume regulatory anion channel and regulating vascular function. This study aims to identify the molecular identity of the endothelial LRRC8 complex and its function in vascular reactivity and blood pressure control. - Source: PubMed
Publication date: 2026/02/04
Yu QiujunZhao YonghuiMaurer JoshuaArullampalam PrakashJohn NathanielTranter John DAbd El-Aziz Tarek MohamedRahimi MehranLin MichelleHalabi Carmen MSah Rajan - We conducted a genome-wide interaction analysis between long-term exposure to trihalomethanes in drinking water and colorectal cancer (CRC) risk in a multicenter case-control study in Spain, including 1037 CRC cases and 2100 controls. Exposure categories were estimated based on sex-specific median and quartile values of total trihalomethanes (TTHM), chloroform (CHCl), and brominated trihalomethanes (Br-THMs) among controls. In addition, TTHM exposure was assessed relative to the WHO guideline thresholds. Gene-environment interaction models were computed with the GxEScanR package. To explore biological plausibility, relevant results were inspected in search of expression quantitative trait loci (eQTLs) in two independent resources: BarcUVaSeq and the Genome Tissue Expression (GTEx) v8. Finally, we searched the Comparative Toxicogenomics Database to identify candidate genes previously linked to trihalomethane exposure, retrieved their eQTLs, and evaluated gene-environment interactions with TTHM levels. We found three variants that modulated CRC risk in relation to CHCl and TTHM exposure: rs77985109 near LRRC8B, chr15:28997737 near WHAMMP2, and rs7890183 near MAGEB2. Two additional variants were specifically found for women and one for rectal cancer. Functional assessment suggested a regulatory role of rs77985109 in LRRC8B expression. Moreover, eQTL analysis of candidate genes revealed an additional variant associated with CCL2 which could modulate CRC risk under different TTHM exposure levels. The present study identified novel loci potentially influencing CRC susceptibility under THM exposure, highlighting the importance of integrating environmental and genetic data to better understand environmental driven cancer risks. Further research is needed to confirm these results and clarify underlying mechanisms. - Source: PubMed
Publication date: 2026/01/11
Moratalla-Navarro FerranObón-Santacana MireiaRius-Sansalvador BlancaGuinó ElisabetMoragas NúriaDonat-Vargas Carolinade Larrea-Baz Nerea FernándezMolina-Barceló AnaGuevara MarcelaMorón-Duran Francisco DDierssen-Sotos TrinidadTardón AdoninaCastaño-Vinyals GemmaCabrera-Castro NataliaMolina Antonio JoséAizpurua AmaiaMorales-Suárez-Varela María MMartín VicenteFernández-Navarro PabloVillanueva Cristina MMoreno Victor - The volume-regulated anion channel (VRAC) is a hetero-hexamer composed of LRRC8A and any of the four other LRRC8 paralogs (LRRC8B-E). Depending on their subunit composition, VRACs not only transport chloride, but also a range of organic substrates including 2'3'-cGAMP (cGAMP). Transfer of this immunomodulator from tumor to host cells is critical for antitumor immunity. Whether this process depends on VRAC in vivo remains incompletely understood. To address this issue, we studied subcutaneous MC38 and B16-F10 tumors in syngeneic mice. Enhanced growth of MC38 tumors lacking cGAMP production confirmed the importance of tumor-produced cGAMP. The impact of VRAC-mediated cGAMP-efflux from tumor cells and its uptake into cells of the tumor microenvironment was investigated using LRRC8A-deficient tumor cells and recipient mice with selective LRRC8 subunit disruptions, respectively. Changed serum cytokines indicated moderate immunomodulatory effects of VRAC-mediated cGAMP export from MC38 tumors. However, tumor growth and the cGAMP-mediated antitumor immune response were independent of both tumor- and host-expressed VRAC. Disruption of any of the non-essential subunits, LRRC8B-LRRC8E, had no discernible effect on T or B cell development in mice. While tumor-produced cGAMP markedly suppresses tumor growth, transport of this immunomodulator to the tumor environment primarily involves transporters distinct from VRAC. - Source: PubMed
Publication date: 2025/12/17
Thöne Fabian M BPolovitskaya Maya MHöpken Uta ERehm ArminJentsch Thomas J - Volume-regulated anion channels (VRACs) are ubiquitously expressed vertebrate ion channels that open in response to hypotonic swelling. VRACs assemble as heteromers of LRRC8A and LRRC8B-E subunits, with different subunit combinations resulting in channels with different properties. Recent studies have described the structures of LRRC8A:C VRACs, but how other VRACs assemble, and which structural features are conserved or variant across channel assemblies remains unknown. Herein, we used cryo-EM to determine structures of a LRRC8A:D VRAC with a 4:2 subunit stoichiometry, which we captured in two conformations. The presence of LRRC8D subunits widens and increases hydrophobicity of the selectivity filter, which may contribute to the unique substrate selectivity of LRRC8D-containing VRACs. The structures reveal lipids bound inside the channel pore, similar to those observed in LRRC8A:C VRACs. We observe that LRRC8D subunit incorporation disrupts packing of the cytoplasmic LRR domains, increasing channel dynamics and opening lateral intersubunit gaps, which we speculate are necessary for pore lipid evacuation and channel activation. Molecular dynamics simulations show that lipids can reside stably within the pore to close the channel. Using electrophysiological experiments, we confirmed that pore lipids block conduction in the closed state, demonstrating that lipid-gating is a general property of VRACs. - Source: PubMed
Publication date: 2025/12/12
Lurie AntonyStephens Christina AKern David MHenn Katharine MLatorraca Naomi RBrohawn Stephen G - Vascular tone is impacted by the endothelium's ability to detect mechanical and chemical stimulation. eucine- ich epeat- ontaining protein A, (LRRC8A), was previously identified as a required component of the mechanoresponsive endothelial LRRC8 complex regulating AKT-endothelial nitric oxide synthase (eNOS) signaling and vascular function. While LRRC8A is broadly expressed, LRRC8B, C, D and E have tissue-restricted expression. Here, we identified 2 single nucleotide polymorphisms (SNPs) in highly associated with elevated diastolic and systolic blood pressure in human genetic studies, implicating LRRC8C as a regulator of vascular function. While LRRC8A/B/C/D/E are expressed in endothelium, co-immunoprecipitation experiments from lung endothelium using -3xFlag knock-in mice, HA knock-in mice and endothelium-specific -3xFlag overexpression mice demonstrate the endothelial LRRC8 complex to be composed largely of LRRC8A/B/C heteromers. knock-out studies in mice and knock-down studies in human umbilical vein endothelial cells show co-dependent expression of LRRC8A/B/C proteins, but not LRRC8D. Functionally, LRRC8A and LRRC8C depletion reduces endothelial volume regulatory anion channel (VRAC) currents, inhibits AKT-eNOS signaling, increases myogenic tone, impairs eNOS dependent vasodilation, and exacerbates angiotensin-induced hypertension. These data identify LRRC8A, LRRC8B and LRRC8C as components of the endothelial LRRC8 complex and reveal LRRC8C as having a non-redundant role in regulating endothelial AKT-eNOS, vascular relaxation and susceptibility to hypertension. - Source: PubMed
Publication date: 2025/08/20
Yu QiujunZhao YonghuiMaurer JoshuaArullampalam PrakashJohn NathanielTranter John DAbd El-Aziz Tarek MohamedLin MichelleLerner Daniel JHalabi Carmen MSah Rajan