Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, United States.
Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, United States.
Biochim Biophys Acta Biomembr. 2021 Mar 1;1863(3):183534. doi: 10.1016/j.bbamem.2020.183534. Epub 2020 Dec 17.
The eukaryotic plasma membrane's lipid composition is found to be ubiquitously asymmetric comparing inner and outer leaflets. This membrane lipid asymmetry plays a crucial role in diverse cellular processes critical for cell survival. A specialized set of transmembrane proteins called translocases, or flippases, have evolved to maintain this membrane lipid asymmetry in an energy-dependent manner. One potential consequence of local variations in membrane lipid asymmetry is membrane remodeling, which is essential for cellular processes such as intracellular trafficking. Recently, there has been a surge in the identification and characterization of flippases, which has significantly advanced the understanding of their functional mechanisms. Furthermore, there are intriguing possibilities for a coupling between membrane curvature and flippase activity. In this review we highlight studies that link membrane shape and remodeling to differential stresses generated by the activity of lipid flippases with an emphasis on data obtained through model membrane systems. We review the common mechanistic models of flippase-mediated lipid flipping and discuss common techniques used to test lipid flippase activity. We then compare the existing data on lipid translocation rates by flippases and conclude with potential future directions for this field.
真核细胞质膜的脂类组成在内外叶层之间普遍存在不对称性。这种膜脂不对称性在许多对细胞生存至关重要的细胞过程中起着关键作用。一组专门的跨膜蛋白，称为转位酶或翻转酶，已经进化为以能量依赖的方式维持这种膜脂不对称性。膜脂不对称性的局部变化的一个潜在后果是膜重塑，这对于细胞内运输等细胞过程是必不可少的。最近，翻转酶的鉴定和特征描述有了突飞猛进的发展，这极大地促进了对其功能机制的理解。此外，膜曲率和翻转酶活性之间存在有趣的耦合可能性。在这篇综述中，我们强调了将膜形状和重塑与脂质翻转酶活性产生的差异压力联系起来的研究，重点介绍了通过模型膜系统获得的数据。我们回顾了翻转酶介导的脂类翻转的常见机制模型，并讨论了用于测试脂类翻转酶活性的常用技术。然后，我们比较了翻转酶的脂类转运率的现有数据，并为该领域的未来发展方向提供了结论。
