Ask about this productRelated genes to: LRRC8E Blocking Peptide
- Gene:
- LRRC8E NIH gene
- Name:
- leucine rich repeat containing 8 VRAC subunit E
- Previous symbol:
- -
- Synonyms:
- FLJ23420
- Chromosome:
- 19p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2005-06-29
- Date modifiied:
- 2018-05-08
Related products to: LRRC8E Blocking Peptide
Related articles to: LRRC8E Blocking Peptide
- 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 - Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer characterized by a high rate of metastasis, poor prognosis, and lack of efficient therapies. KBU2046, a small molecule inhibitor, can inhibit cell motility in malignant tumors, including breast cancer. However, the specific targets and the corresponding mechanism of its function remain unclear. - Source: PubMed
Publication date: 2024/10/16
Chen JinxiaDai SuliZhang GengWei SisiZhao XuetaoZheng YangWang YaojieWang XiaohanLiu YunjiangZhao Lianmei - The volume-regulated anion channel (VRAC) is formed by LRRC8 subunits. Besides their role in the maintenance of cell homeostasis, VRACs are critically involved in oxidative stress mechanisms: reactive oxygen species directly modulate VRACs in a subunit-dependent manner. It was reported that LRRC8A-LRRC8E heteromeric channels are activated by oxidation, whereas LRRC8A-LRRC8C heteromers are inhibited. Here we adopted chimeric- as well as concatemeric-based strategies to identify residues responsible for the divergent effect of oxidants. We identified two cysteines in the first two leucine rich repeats of LRRC8E, C424 and C448, as the targets of oxidation. Oxidation likely results in the formation of a disulfide bond between the two cysteines, which in turn induces a conformational change leading to channel activation. Additionally, we found that LRRC8C inhibition is caused by oxidation of the first methionine. We thus identified crucial molecular elements involved in channel activation, which are conceivably relevant in determining physiological ROS effects. KEY POINTS: Volume-regulated anion channels (VRACs) are heterohexameric complexes composed of an essential LRRC8A subunit and a variable number of LRRC8B-E subunits. VRACs are directly regulated by oxidation, with LRRC8A-LRRC8E heteromers being potentiated and LRRC8A-LRRC8C heteromers being inhibited by oxidation. We identified two LRRC8E specific intracellular cysteines that form a disulfide bond upon oxidation leading to LRRC8A-LRRC8E potentiation. Inhibition of LRRC8A-LRRC8C heteromers is mediated by the oxidation of the start methionine, being additionally dependent on the identity of the LRR domain. Besides providing physiological insights concerning the outcome of reactive oxygen species modulation, the results point to key structural elements involved in VRAC activation. - Source: PubMed
Publication date: 2022/08/05
Bertelli SaraZuccolini PaoloGavazzo PaolaPusch Michael - Volume-regulated anion channels (VRACs) are heterohexamers of LRRC8A with LRRC8B, -C, -D, or -E in various combinations. Depending on the subunit composition, these swelling-activated channels conduct chloride, amino acids, organic osmolytes, and drugs. Despite VRACs' role in cell volume regulation, and large osmolarity changes in the kidney, neither the localization nor the function of VRACs in the kidney is known. - Source: PubMed
Publication date: 2022/07/01
López-Cayuqueo Karen IPlanells-Cases RosaPietzke MatthiasOliveras AnnaKempa StefanBachmann SebastianJentsch Thomas J - LINC00511 has been reported as a biomarker related to the prognosis of non-small cell lung cancer (NSCLC), but the molecular mechanism and exact functions of LINC00511 in chemoresistance of NSCLC remain to be elucidated. - Source: PubMed
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