Zwaal R F A, Comfurius P, Bevers E M
Dept of Biochemistry, Cardiovascular Research Institute Maastricht CARIM, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, Netherlands.
Cell Mol Life Sci. 2005 May;62(9):971-88. doi: 10.1007/s00018-005-4527-3.
The asymmetric phospholipid distribution in plasma membranes is normally maintained by energy-dependent lipid transporters that translocate different phospholipids from one monolayer to the other against their respective concentration gradients. When cells are activated, or enter apoptosis, lipid asymmetry can be perturbed by other lipid transporters (scramblases) that shuttle phospholipids non-specifically between the two monolayers. This exposes phosphatidylserine (PS) at the cells' outer surface. Since PS promotes blood coagulation, defective scramblase activity upon platelet stimulation causes a bleeding disorder (Scott syndrome). PS exposure also plays a pivotal role in the recognition and removal of apoptotic cells via a PS-recognizing receptor on phagocytic cells. Furthermore, expression of PS at the cell surface can occur in a wide variety of disorders. This review aims at highlighting how PS expression in different cells may complicate a variety of pathological conditions, including those that promote thromboembolic complications or produce aberrations in apoptotic cell removal.
质膜中不对称的磷脂分布通常由能量依赖性脂质转运蛋白维持,这些转运蛋白能逆着各自的浓度梯度将不同的磷脂从一个单分子层转运到另一个单分子层。当细胞被激活或进入凋亡状态时,脂质不对称性会受到其他脂质转运蛋白(翻转酶)的干扰,这些翻转酶能在两个单分子层之间非特异性地穿梭磷脂。这会使磷脂酰丝氨酸(PS)暴露在细胞外表面。由于PS促进血液凝固,血小板刺激时翻转酶活性缺陷会导致出血性疾病(斯科特综合征)。PS暴露在通过吞噬细胞上的PS识别受体识别和清除凋亡细胞过程中也起着关键作用。此外,PS在细胞表面的表达可发生在多种疾病中。本综述旨在强调不同细胞中PS的表达如何使多种病理状况复杂化,包括那些促进血栓栓塞并发症或导致凋亡细胞清除异常的状况。