Hankins Hannah M, Baldridge Ryan D, Xu Peng, Graham Todd R
Department of Biological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37235, USA.
Traffic. 2015 Jan;16(1):35-47. doi: 10.1111/tra.12233. Epub 2014 Nov 5.
It is well known that lipids are heterogeneously distributed throughout the cell. Most lipid species are synthesized in the endoplasmic reticulum (ER) and then distributed to different cellular locations in order to create the distinct membrane compositions observed in eukaryotes. However, the mechanisms by which specific lipid species are trafficked to and maintained in specific areas of the cell are poorly understood and constitute an active area of research. Of particular interest is the distribution of phosphatidylserine (PS), an anionic lipid that is enriched in the cytosolic leaflet of the plasma membrane. PS transport occurs by both vesicular and non-vesicular routes, with members of the oxysterol-binding protein family (Osh6 and Osh7) recently implicated in the latter route. In addition, the flippase activity of P4-ATPases helps build PS membrane asymmetry by preferentially translocating PS to the cytosolic leaflet. This asymmetric PS distribution can be used as a signaling device by the regulated activation of scramblases, which rapidly expose PS on the extracellular leaflet and play important roles in blood clotting and apoptosis. This review will discuss recent advances made in the study of phospholipid flippases, scramblases and PS-specific lipid transfer proteins, as well as how these proteins contribute to subcellular PS distribution.
众所周知，脂质在整个细胞中呈异质分布。大多数脂质种类在内质网（ER）中合成，然后分布到不同的细胞位置，以形成真核生物中观察到的独特膜组成。然而，特定脂质种类被运输到细胞特定区域并在其中维持的机制仍知之甚少，是一个活跃的研究领域。特别令人感兴趣的是磷脂酰丝氨酸（PS）的分布，PS是一种阴离子脂质，在质膜的胞质小叶中富集。PS的运输通过囊泡和非囊泡途径进行，氧甾醇结合蛋白家族的成员（Osh6和Osh7）最近被认为参与了后者途径。此外，P4-ATP酶的翻转酶活性通过优先将PS转运到胞质小叶来帮助建立PS膜不对称性。这种不对称的PS分布可通过调节激活磷脂翻转酶用作信号装置，磷脂翻转酶会迅速将PS暴露在细胞外小叶上，并在血液凝固和细胞凋亡中发挥重要作用。本综述将讨论磷脂翻转酶、磷脂翻转酶和PS特异性脂质转运蛋白研究的最新进展，以及这些蛋白质如何促进亚细胞PS分布。
