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
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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。
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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.

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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.
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