Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands; and Department of Biology, Amherst College, Amherst, Massachusetts.
Physiol Rev. 2016 Apr;96(2):605-45. doi: 10.1152/physrev.00020.2015.
Phosphatidylserine (PS) is a major component of membrane bilayers whose change in distribution between inner and outer leaflets is an important physiological signal. Normally, members of the type IV P-type ATPases spend metabolic energy to create an asymmetric distribution of phospholipids between the two leaflets, with PS confined to the cytoplasmic membrane leaflet. On occasion, membrane enzymes, known as scramblases, are activated to facilitate transbilayer migration of lipids, including PS. Recently, two proteins required for such randomization have been identified: TMEM16F, a scramblase regulated by elevated intracellular Ca(2+), and XKR8, a caspase-sensitive protein required for PS exposure in apoptotic cells. Once exposed at the cell surface, PS regulates biochemical reactions involved in blood coagulation, and bone mineralization, and also regulates a variety of cell-cell interactions. Exposed on the surface of apoptotic cells, PS controls their recognition and engulfment by other cells. This process is exploited by parasites to invade their host, and in specialized form is used to maintain photoreceptors in the eye and modify synaptic connections in the brain. This review discusses what is known about the mechanism of PS exposure at the surface of the plasma membrane of cells, how actors in the extracellular milieu sense surface exposed PS, and how this recognition is translated to downstream consequences of PS exposure.
磷脂酰丝氨酸（PS）是膜双层的主要成分，其在内外叶之间的分布变化是一个重要的生理信号。通常，IV 型 P 型 ATP 酶的成员会花费代谢能量来在两个叶之间创建磷脂的不对称分布，PS 局限于质膜叶。有时，称为翻转酶的膜酶被激活以促进脂质（包括 PS）的跨双层迁移。最近，已经确定了两种用于这种随机化的蛋白质：TMEM16F，一种受细胞内 Ca(2+)升高调节的翻转酶，以及 XKR8，一种在凋亡细胞中 PS 暴露所必需的半胱天冬酶敏感蛋白。一旦在细胞表面暴露，PS 调节涉及血液凝固和骨矿化的生化反应，并调节各种细胞-细胞相互作用。在凋亡细胞的表面暴露的 PS 控制其他细胞对其的识别和吞噬。寄生虫利用这个过程来入侵宿主，而在特殊形式中，它被用于维持眼睛中的光感受器和修饰大脑中的突触连接。这篇综述讨论了细胞质膜表面 PS 暴露的机制、细胞外环境中的哪些因素可以感知到表面暴露的 PS 以及这种识别如何转化为 PS 暴露的下游后果。
