The C. elegans Hypertonic Stress Response: Big Insights from Shrinking Worms.

The C. elegans Hypertonic Stress Response: Big Insights from Shrinking Worms.
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DOI:
10.33594/000000332
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发表时间:
2021-02-25
期刊:
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
影响因子:
--
通讯作者:
Lamitina T
Lamitina T
中科院分区:
其他
文献类型:
--
作者:
Urso SJ;Lamitina T

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细胞体积是生物学中最具攻击性的生理设定值之一。细胞内离子和水浓度的变化是由代谢或环境暴露的变化引起的,会破坏蛋白质折叠、酶活性和大分子组装。为了应对这些挑战,细胞和生物体已经进化出多方面的、进化上保守的分子机制来恢复细胞体积和修复应激引起的损伤。然而,关于细胞体积“感知”的本质以及激活生理反应机制所涉及的分子信号通路,仍有许多未解之谜。模式生物秀丽隐杆线虫的无偏遗传筛选为这些问题提供了新的和意想不到的见解,特别是与高渗应激反应(HTSR)途径有关的问题。秀丽隐杆线虫HTSR通路的一个令人惊讶的特征是,它受到参与蛋白质稳态和细胞外基质(ECM)的蛋白质的强烈负调控。ECM的作用特别强调了在保存原生ECM组织关联的活生物体背景下研究HTSR的重要性。最近发现的第二个新特征是HTSR在转录后水平受到调节。本综述的目的是描述这些发现,为其含义提供背景,并提出悬而未决的问题来指导未来的研究。
Cell volume is one of the most aggressively defended physiological set points in biology. Changes in intracellular ion and water concentrations, which are induced by changes in metabolism or environmental exposures, disrupt protein folding, enzymatic activity, and macromolecular assemblies. To counter these challenges, cells and organisms have evolved multifaceted, evolutionarily conserved molecular mechanisms to restore cell volume and repair stress induced damage. However, many unanswered questions remain regarding the nature of cell volume ‘sensing’ as well as the molecular signaling pathways involved in activating physiological response mechanisms. Unbiased genetic screening in the model organism C. elegans is providing new and unexpected insights into these questions, particularly questions relating to the hypertonic stress response (HTSR) pathway. One surprising characteristic of the HTSR pathway in C. elegans is that it is under strong negative regulation by proteins involved in protein homeostasis and the extracellular matrix (ECM). The role of the ECM in particular highlights the importance of studying the HTSR in the context of a live organism where native ECM-tissue associations are preserved. A second novel and recently discovered characteristic is that the HTSR is regulated at the post-transcriptional level. The goal of this review is to describe these discoveries, to provide context for their implications, and to raise outstanding questions to guide future research.
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