Specific and essential but not sufficient roles of LRRC8A in the activity of volume-sensitive outwardly rectifying anion channel (VSOR)

IF 3.3 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Toshiaki Okada, Md. Rafiqul Islam, N. Tsiferova, Y. Okada, R. Sabirov
{"title":"Specific and essential but not sufficient roles of LRRC8A in the activity of volume-sensitive outwardly rectifying anion channel (VSOR)","authors":"Toshiaki Okada, Md. Rafiqul Islam, N. Tsiferova, Y. Okada, R. Sabirov","doi":"10.1080/19336950.2016.1247133","DOIUrl":null,"url":null,"abstract":"ABSTRACT The broadly expressed volume-sensitive outwardly rectifying anion channel (VSOR, also called VRAC) plays essential roles in cell survival and death. Recent findings have suggested that LRRC8A is a core component of VSOR in human cells. In the present study, VSOR currents were found to be largely reduced by siRNA against LRRC8A in mouse C127 cells as well. In contrast, LRRC8A knockdown never affected activities of 4 other types of anion channel activated by acid, Ca2+, patch excision or cAMP. While cisplatin-resistant KCP-4 cells poorly expressed endogenous VSOR activity, molecular expression levels of LRRC8A, LRRC8D and LRRC8E were indistinguishable between VSOR-deficient KCP-4 cells and the parental VSOR-rich KB cells. Furthermore, overexpression of LRRC8A alone or together with LRRC8D or LRRC8E in KCP-4 cells failed to restore VSOR activity. These results show that deficiency of VSOR currents in KCP-4 cells is not due to insufficient expression of the LRRC8A/D/E gene, suggesting an essential involvement of some other factor(s), and indicate that further study is required to better understand the complexities of the molecular determinants of VSOR, including the precise role of LRRC8 proteins.","PeriodicalId":9750,"journal":{"name":"Channels","volume":"1 1","pages":"109 - 120"},"PeriodicalIF":3.3000,"publicationDate":"2017-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"27","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Channels","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/19336950.2016.1247133","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 27

Abstract

ABSTRACT The broadly expressed volume-sensitive outwardly rectifying anion channel (VSOR, also called VRAC) plays essential roles in cell survival and death. Recent findings have suggested that LRRC8A is a core component of VSOR in human cells. In the present study, VSOR currents were found to be largely reduced by siRNA against LRRC8A in mouse C127 cells as well. In contrast, LRRC8A knockdown never affected activities of 4 other types of anion channel activated by acid, Ca2+, patch excision or cAMP. While cisplatin-resistant KCP-4 cells poorly expressed endogenous VSOR activity, molecular expression levels of LRRC8A, LRRC8D and LRRC8E were indistinguishable between VSOR-deficient KCP-4 cells and the parental VSOR-rich KB cells. Furthermore, overexpression of LRRC8A alone or together with LRRC8D or LRRC8E in KCP-4 cells failed to restore VSOR activity. These results show that deficiency of VSOR currents in KCP-4 cells is not due to insufficient expression of the LRRC8A/D/E gene, suggesting an essential involvement of some other factor(s), and indicate that further study is required to better understand the complexities of the molecular determinants of VSOR, including the precise role of LRRC8 proteins.
LRRC8A在体积敏感外向整流阴离子通道(VSOR)活性中的特异、必要但不充分的作用
广泛表达的体积敏感外向整流阴离子通道(VSOR,也称为VRAC)在细胞生存和死亡中起着重要作用。最近的研究表明,LRRC8A是人类细胞中VSOR的核心成分。在本研究中,我们发现在小鼠C127细胞中,siRNA对LRRC8A的作用也大大降低了VSOR电流。相比之下,LRRC8A敲低不影响酸、Ca2+、斑块切除或cAMP激活的其他4种阴离子通道的活性。虽然顺铂耐药KCP-4细胞内源性VSOR活性表达较差,但在VSOR缺失的KCP-4细胞和亲代VSOR丰富的KB细胞中,LRRC8A、LRRC8D和LRRC8E的分子表达水平无法区分。此外,在KCP-4细胞中,LRRC8A单独或与LRRC8D或LRRC8E过表达都不能恢复VSOR的活性。这些结果表明,KCP-4细胞中VSOR电流的缺乏并不是因为LRRC8A/D/E基因表达不足,而可能与其他一些因素有关,并表明需要进一步研究以更好地了解VSOR分子决定因素的复杂性,包括LRRC8蛋白的确切作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Channels
Channels 生物-生化与分子生物学
CiteScore
5.90
自引率
0.00%
发文量
21
审稿时长
6-12 weeks
期刊介绍: Channels is an open access journal for all aspects of ion channel research. The journal publishes high quality papers that shed new light on ion channel and ion transporter/exchanger function, structure, biophysics, pharmacology, and regulation in health and disease. Channels welcomes interdisciplinary approaches that address ion channel physiology in areas such as neuroscience, cardiovascular sciences, cancer research, endocrinology, and gastroenterology. Our aim is to foster communication among the ion channel and transporter communities and facilitate the advancement of the field.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信