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A Genetic Titration of Membrane Composition in C. elegans Reveals its Importance for Multiple Cellular and Physiological Traits.
GENETICS ( IF 3.3 ) Pub Date : 2021-06-14 , DOI: 10.1093/genetics/iyab093
Ranjan Devkota 1 , Delaney Kaper 1 , Rakesh Bodhicharla 1 , Marcus Henricsson 2 , Jan Borén 2 , Marc Pilon 1
Affiliation  

The composition and biophysical properties of cellular membranes must be tightly regulated to maintain the proper functions of myriad processes within cells. To better understand the importance of membrane homeostasis, we assembled a panel of five C. elegans strains that show a wide span of membrane composition and properties, ranging from excessively rich in saturated fatty acids (SFAs) and rigid to excessively rich in polyunsaturated fatty acids (PUFAs) and fluid. The genotypes of the five strain are, from most rigid to most fluid: paqr-1(tm3262);paqr-2(tm3410), paqr-2(tm3410), N2 (wild-type), mdt-15(et14);nhr-49(et8), and mdt-15(et14);nhr-49(et8);acs-13(et54). We confirmed the excess SFA/rigidity-to-excess PUFA/fluid gradient using the methods of fluorescence recovery after photobleaching (FRAP) and lipidomics analysis. The five strains were then studied for a variety of cellular and physiological traits and found to exhibit defects in: permeability, lipid peroxidation, growth at different temperatures, tolerance to SFA-rich diets, lifespan, brood size, vitellogenin trafficking, oogenesis and autophagy during starvation. The excessively rigid strains often exhibited defects in opposite directions compared to the excessively fluid strains. We conclude that deviation from wild-type membrane homeostasis is pleiotropically deleterious for numerous cellular/physiological traits. The strains introduced here should prove useful to further study the cellular and physiological consequences of impaired membrane homeostasis.

中文翻译:


线虫膜成分的遗传滴定揭示了其对多种细胞和生理特征的重要性。



细胞膜的组成和生物物理特性必须受到严格调节,以维持细胞内无数过程的正常功能。为了更好地了解膜稳态的重要性,我们组装了五个秀丽隐杆线虫菌株,这些菌株显示出广泛的膜组成和特性,从过度富含饱和脂肪酸(SFA)和刚性到过度富含多不饱和脂肪酸(PUFA)和液体。五个菌株的基因型从最刚性到最流动依次为:paqr-1(tm3262);paqr-2(tm3410)、paqr-2(tm3410)、N2(野生型)、mdt-15(et14); nhr-49(et8) 和 mdt-15(et14);nhr-49(et8);acs-13(et54)。我们使用光漂白后荧光恢复 (FRAP) 和脂质组学分析的方法确认了过量的 SFA/刚性到过量的 PUFA/流体梯度。然后对这五种菌株的各种细胞和生理特征进行了研究,发现它们在以下方面表现出缺陷:渗透性、脂质过氧化、不同温度下的生长、对富含 SFA 的饮食的耐受性、寿命、孵化大小、卵黄蛋白原运输、卵子发生和自噬。饥饿。与过度流体应变相比,过度刚性应变通常会在相反方向表现出缺陷。我们得出的结论是,偏离野生型膜稳态对于许多细胞/生理特征来说是多效性有害的。这里介绍的菌株应该有助于进一步研究膜稳态受损的细胞和生理后果。
更新日期:2021-06-17
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