Phosphatidylethanolamine Is a Key Regulator of Membrane Fluidity in Eukaryotic Cells

Phosphatidylethanolamine Is a Key Regulator of Membrane Fluidity in Eukaryotic Cells
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DOI:
10.1074/jbc.m115.706523
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发表时间:
2016-02-12
影响因子:
4.8
通讯作者:
Govaerts, Cedric
Govaerts, Cedric
中科院分区:
生物学2区
文献类型:
--
作者:
Dawaliby, Rosie;Trubbia, Cataldo;Govaerts, Cedric

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适当的膜流动性是各种关键细胞过程所必需的,特别是膜蛋白的正常功能。在大多数真核细胞中,膜流动性已知由脂肪酸去饱和和胆固醇调节,尽管一些细胞,如昆虫细胞,几乎没有甾醇合成。我们在这里表明,昆虫和哺乳动物细胞在各自的生理温度下呈现相似的微粘度。为了研究甾醇和磷脂如何控制流动性稳态,我们在正常或甾醇修饰的条件下定量了昆虫SF9和哺乳动物HEK 293 T细胞的脂质组成。正如预期的那样,与哺乳动物细胞相比,昆虫细胞显示出最少的固醇。当磷脂酰乙醇胺(PE)与磷脂酰胆碱(PC)的比例倒置时(在SF9细胞中高4倍),还观察到磷脂含量的主要差异。脂质体的体外研究证实,胆固醇和PE都可以增加双层的刚性,这表明两者都可以被细胞用来维持膜的流动性。然后,我们表明,外源性增加SF9膜中的胆固醇量导致PE:PC比率显著降低,而使用他汀类药物治疗降低HEK 293 T细胞中的胆固醇导致PE:PC比率增加。在所有情况下,膜流动性得以维持,表明两种细胞类型通过固醇和磷脂的联合收割机调节来控制适当的膜流动性。
Adequate membrane fluidity is required for a variety of key cellular processes and in particular for proper function of membrane proteins. In most eukaryotic cells, membrane fluidity is known to be regulated by fatty acid desaturation and cholesterol, although some cells, such as insect cells, are almost devoid of sterol synthesis. We show here that insect and mammalian cells present similar microviscosity at their respective physiological temperature. To investigate how both sterols and phospholipids control fluidity homeostasis, we quantified the lipidic composition of insect SF9 and mammalian HEK 293T cells under normal or sterol-modified condition. As expected, insect cells show minimal sterols compared with mammalian cells. A major difference is also observed in phospholipid content as the ratio of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) is inverted (4 times higher in SF9 cells). In vitro studies in liposomes confirm that both cholesterol and PE can increase rigidity of the bilayer, suggesting that both can be used by cells to maintain membrane fluidity. We then show that exogenously increasing the cholesterol amount in SF9 membranes leads to a significant decrease in PE:PC ratio whereas decreasing cholesterol in HEK 293T cells using statin treatment leads to an increase in the PE:PC ratio. In all cases, the membrane fluidity is maintained, indicating that both cell types combine regulation by sterols and phospholipids to control proper membrane fluidity.