{"title":"应对细胞损伤引起的钙超载:ER的救星。","authors":"Goutam Chandra, Davi A G Mázala, 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, Davi A G Mázala, 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}
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.
Cell StressBiochemistry, 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.