van Genderen Hugo O, Kenis Heidi, Hofstra Leo, Narula Jagat, Reutelingsperger Chris P M
Department of Biochemistry, Cardiovascular Research Institute Maastricht, University Maastricht, Maastricht, The Netherlands.
Biochim Biophys Acta. 2008 Jun;1783(6):953-63. doi: 10.1016/j.bbamcr.2008.01.030. Epub 2008 Feb 20.
In normal healthy cells phosphatidylserine is located in the inner leaflet of the plasma membrane. However, on activated platelets, dying cells and under specific circumstances also on various types of viable leukocytes phosphatidylserine is actively externalized to the outer leaflet of the plasma membrane. Annexin A5 has the ability to bind in a calcium-dependent manner to phosphatidylserine and to form a membrane-bound two-dimensional crystal lattice. Based on these abilities various functions for extracellular annexin A5 on the phosphatidylserine-expressing plasma membrane have been proposed. In this review we describe possible mechanisms for externalization of annexin A5 and various processes in which extracellular annexin A5 may play a role such as blood coagulation, apoptosis, phagocytosis and formation of plasma membrane-derived microparticles. We further highlight the recent discovery of internalization of extracellular annexin A5 by phosphatidylserine-expressing cells.
在正常健康细胞中,磷脂酰丝氨酸位于质膜的内小叶。然而,在活化的血小板、濒死细胞以及特定情况下,各种类型的存活白细胞上的磷脂酰丝氨酸也会主动外翻至质膜的外小叶。膜联蛋白A5能够以钙依赖的方式与磷脂酰丝氨酸结合,并形成膜结合的二维晶格。基于这些特性,人们提出了细胞外膜联蛋白A5在表达磷脂酰丝氨酸的质膜上的各种功能。在本综述中,我们描述了膜联蛋白A5外翻的可能机制以及细胞外膜联蛋白A5可能发挥作用的各种过程,如血液凝固、细胞凋亡、吞噬作用和质膜衍生微粒的形成。我们还进一步强调了最近关于表达磷脂酰丝氨酸的细胞内化细胞外膜联蛋白A5的发现。