应对细胞损伤引起的钙超载:ER的救星。

IF 4.1 Q2 CELL BIOLOGY Cell Stress Pub Date : 2021-04-16 DOI:10.15698/cst2021.05.249
Goutam Chandra, Davi A G Mázala, Jyoti K Jaiswal
{"title":"应对细胞损伤引起的钙超载:ER的救星。","authors":"Goutam Chandra,&nbsp;Davi A G Mázala,&nbsp;Jyoti K Jaiswal","doi":"10.15698/cst2021.05.249","DOIUrl":null,"url":null,"abstract":"<p><p>Cells maintain their cytosolic calcium (Ca<sup>2+</sup>) in nanomolar range and use controlled increase in Ca<sup>2+</sup> for intracellular signaling. With the extracellular Ca<sup>2+</sup> in the millimolar range, there is a steep Ca<sup>2+</sup> gradient across the plasma membrane (PM). Thus, injury that damages PM, leads to a cytosolic Ca<sup>2+</sup> overload, which helps activate PM repair (PMR) response. However, in order to survive, the cells must cope with the Ca<sup>2+</sup> overload. In a recent study (Chandra <i>et al.</i> J Cell Biol, doi: 10.1083/jcb.202006035) we have examined how cells cope with injury-induced cytosolic Ca<sup>2+</sup> overload. By monitoring Ca<sup>2+</sup> dynamics in the cytosol and endoplasmic reticulum (ER), we found that PM injury-triggered increase in cytosolic Ca<sup>2+</sup> is taken up by the ER. Pharmacological inhibition of ER Ca<sup>2+</sup> uptake interferes with this process and compromises the repair ability of the injured cells. Muscle cells from patients and mouse model for the muscular dystrophy showed that lack of Anoctamin 5 (ANO5)/Transmembrane protein 16E (TMEM16E), an ER-resident putative Ca<sup>2+</sup>-activated chloride channel (CaCC), are poor at coping with cytosolic Ca<sup>2+</sup> overload. Pharmacological inhibition of CaCC and lack of ANO5, both prevent Ca<sup>2+</sup> uptake into ER. These studies identify a requirement of Cl<sup>-</sup> uptake by the ER in sequestering injury-triggered cytosolic Ca<sup>2+</sup> increase in the ER. Further, these studies show that ER helps injured cells cope with Ca<sup>2+</sup> overload during PMR, lack of which contributes to muscular dystrophy due to mutations in the ANO5 protein.</p>","PeriodicalId":36371,"journal":{"name":"Cell Stress","volume":"5 5","pages":"73-75"},"PeriodicalIF":4.1000,"publicationDate":"2021-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090859/pdf/","citationCount":"3","resultStr":"{\"title\":\"Coping with the calcium overload caused by cell injury: ER to the rescue.\",\"authors\":\"Goutam Chandra,&nbsp;Davi A G Mázala,&nbsp;Jyoti K Jaiswal\",\"doi\":\"10.15698/cst2021.05.249\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cells maintain their cytosolic calcium (Ca<sup>2+</sup>) in nanomolar range and use controlled increase in Ca<sup>2+</sup> for intracellular signaling. With the extracellular Ca<sup>2+</sup> in the millimolar range, there is a steep Ca<sup>2+</sup> gradient across the plasma membrane (PM). Thus, injury that damages PM, leads to a cytosolic Ca<sup>2+</sup> overload, which helps activate PM repair (PMR) response. However, in order to survive, the cells must cope with the Ca<sup>2+</sup> overload. In a recent study (Chandra <i>et al.</i> J Cell Biol, doi: 10.1083/jcb.202006035) we have examined how cells cope with injury-induced cytosolic Ca<sup>2+</sup> overload. By monitoring Ca<sup>2+</sup> dynamics in the cytosol and endoplasmic reticulum (ER), we found that PM injury-triggered increase in cytosolic Ca<sup>2+</sup> is taken up by the ER. Pharmacological inhibition of ER Ca<sup>2+</sup> uptake interferes with this process and compromises the repair ability of the injured cells. Muscle cells from patients and mouse model for the muscular dystrophy showed that lack of Anoctamin 5 (ANO5)/Transmembrane protein 16E (TMEM16E), an ER-resident putative Ca<sup>2+</sup>-activated chloride channel (CaCC), are poor at coping with cytosolic Ca<sup>2+</sup> overload. Pharmacological inhibition of CaCC and lack of ANO5, both prevent Ca<sup>2+</sup> uptake into ER. These studies identify a requirement of Cl<sup>-</sup> uptake by the ER in sequestering injury-triggered cytosolic Ca<sup>2+</sup> increase in the ER. Further, these studies show that ER helps injured cells cope with Ca<sup>2+</sup> overload during PMR, lack of which contributes to muscular dystrophy due to mutations in the ANO5 protein.</p>\",\"PeriodicalId\":36371,\"journal\":{\"name\":\"Cell Stress\",\"volume\":\"5 5\",\"pages\":\"73-75\"},\"PeriodicalIF\":4.1000,\"publicationDate\":\"2021-04-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8090859/pdf/\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Stress\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.15698/cst2021.05.249\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Stress","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.15698/cst2021.05.249","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 3

摘要

细胞维持其胞质钙(Ca2+)在纳摩尔范围内,并使用Ca2+的控制增加细胞内信号传导。随着细胞外Ca2+在毫摩尔范围内,有一个陡峭的Ca2+梯度穿过质膜(PM)。因此,损伤PM,导致细胞质Ca2+超载,这有助于激活PM修复(PMR)反应。然而,为了生存,细胞必须应对Ca2+超载。在最近的一项研究中(钱德拉等人)。J细胞生物学,doi: 10.1083/jcb.202006035),我们已经研究了细胞如何应对损伤诱导的细胞质Ca2+超载。通过监测细胞质和内质网(ER)中的Ca2+动态,我们发现PM损伤引发的细胞质Ca2+增加被ER吸收。ER Ca2+摄取的药理学抑制干扰了这一过程,损害了受损细胞的修复能力。来自肌肉萎缩症患者和小鼠模型的肌肉细胞显示,缺乏氨基五(ANO5)/跨膜蛋白16E (TMEM16E),一种驻扎在er的假定的Ca2+激活氯离子通道(CaCC),在应对胞质Ca2+过载方面表现不佳。CaCC的药理抑制和ANO5的缺乏,都阻止Ca2+摄取到内质网。这些研究确定了内质网对Cl-摄取的要求,以隔离内质网中损伤引发的胞质Ca2+增加。此外,这些研究表明,内质网有助于受损细胞在PMR期间应对Ca2+超载,由于ANO5蛋白突变,缺乏Ca2+会导致肌肉萎缩。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Coping with the calcium overload caused by cell injury: ER to the rescue.

Cells maintain their cytosolic calcium (Ca2+) in nanomolar range and use controlled increase in Ca2+ for intracellular signaling. With the extracellular Ca2+ in the millimolar range, there is a steep Ca2+ gradient across the plasma membrane (PM). Thus, injury that damages PM, leads to a cytosolic Ca2+ overload, which helps activate PM repair (PMR) response. However, in order to survive, the cells must cope with the Ca2+ overload. In a recent study (Chandra et al. J Cell Biol, doi: 10.1083/jcb.202006035) we have examined how cells cope with injury-induced cytosolic Ca2+ overload. By monitoring Ca2+ dynamics in the cytosol and endoplasmic reticulum (ER), we found that PM injury-triggered increase in cytosolic Ca2+ is taken up by the ER. Pharmacological inhibition of ER Ca2+ uptake interferes with this process and compromises the repair ability of the injured cells. Muscle cells from patients and mouse model for the muscular dystrophy showed that lack of Anoctamin 5 (ANO5)/Transmembrane protein 16E (TMEM16E), an ER-resident putative Ca2+-activated chloride channel (CaCC), are poor at coping with cytosolic Ca2+ overload. Pharmacological inhibition of CaCC and lack of ANO5, both prevent Ca2+ uptake into ER. These studies identify a requirement of Cl- uptake by the ER in sequestering injury-triggered cytosolic Ca2+ increase in the ER. Further, these studies show that ER helps injured cells cope with Ca2+ overload during PMR, lack of which contributes to muscular dystrophy due to mutations in the ANO5 protein.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Cell Stress
Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
13.50
自引率
0.00%
发文量
21
审稿时长
15 weeks
期刊介绍: Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.
期刊最新文献
Dynamics of cell membrane lesions and adaptive conductance under the electrical stress. Saliva, a molecular reflection of the human body? Implications for diagnosis and treatment. CircRNA regulates the liquid-liquid phase separation of ATG4B, a novel strategy to inhibit cancer metastasis? Pathogenic hyperactivation of mTORC1 by cytoplasmic EP300 in Hutchinson-Gilford progeria syndrome. The missing hallmark of health: psychosocial adaptation.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1