Chauhan Neha, Farine Luce, Pandey Kalpana, Menon Anant K, Bütikofer Peter
Department of Biochemistry, Weill Cornell Medical College, New York 10065, USA.
Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland.
Biochim Biophys Acta. 2016 Aug;1861(8 Pt B):757-766. doi: 10.1016/j.bbalip.2016.02.025. Epub 2016 Mar 2.
Glycerophospholipids are the principal fabric of cellular membranes. The pathways by which these lipids are synthesized were elucidated mainly through the work of Kennedy and colleagues in the late 1950s and early 1960s. Subsequently, attention turned to cell biological aspects of lipids: Where in the cell are lipids synthesized? How are lipids integrated into membranes to form a bilayer? How are they sorted and transported from their site of synthesis to other cellular destinations? These topics, collectively termed 'lipid topogenesis', were the subject of a review article in 1981 by Bell, Ballas and Coleman. We now assess what has been learned about early events of lipid topogenesis, i.e. "lipid synthesis, the integration of lipids into membranes, and lipid translocation across membranes", in the 35 years since the publication of this important review. We highlight the recent elucidation of the X-ray structures of key membrane enzymes of glycerophospholipid synthesis, progress on identifying lipid scramblase proteins needed to equilibrate lipids across membranes, and new complexities in the subcellular location and membrane topology of phosphatidylinositol synthesis revealed through a comparison of two unicellular model eukaryotes. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.
甘油磷脂是细胞膜的主要组成部分。这些脂质的合成途径主要是通过肯尼迪及其同事在20世纪50年代末和60年代初的研究得以阐明的。随后，人们的注意力转向了脂质的细胞生物学方面：脂质在细胞的什么部位合成？脂质如何整合到膜中形成双层结构？它们如何从合成部位分选并运输到细胞的其他部位？这些主题统称为“脂质拓扑发生”，是贝尔、巴拉斯和科尔曼在1981年发表的一篇综述文章的主题。我们现在评估自这篇重要综述发表以来的35年里，在脂质拓扑发生的早期事件方面，即“脂质合成、脂质整合到膜中以及脂质跨膜转运”，我们学到了什么。我们强调了最近对甘油磷脂合成关键膜酶的X射线结构的阐明、在鉴定跨膜平衡脂质所需的脂质翻转酶蛋白方面取得的进展，以及通过比较两种单细胞模式真核生物揭示的磷脂酰肌醇合成在亚细胞定位和膜拓扑结构方面的新复杂性。本文是名为《细胞脂质景观》的特刊的一部分，由蒂姆·P·莱文和阿南特·K·梅农编辑。
