Wang Xiaochen, Wang Jin, Gengyo-Ando Keiko, Gu Lichuan, Sun Chun-Ling, Yang Chonglin, Shi Yong, Kobayashi Tetsuo, Shi Yigong, Mitani Shohei, Xie Xiao-Song, Xue Ding
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Nat Cell Biol. 2007 May;9(5):541-9. doi: 10.1038/ncb1574. Epub 2007 Apr 1.
Externalization of phosphatidylserine, which is normally restricted to the inner leaflet of plasma membrane, is a hallmark of mammalian apoptosis. It is not known what activates and mediates the phosphatidylserine externalization process in apoptotic cells. Here, we report the development of an annexin V-based phosphatidylserine labelling method and show that a majority of apoptotic germ cells in Caenorhabditis elegans have surface-exposed phosphatidylserine, indicating that phosphatidylserine externalization is a conserved apoptotic event in worms. Importantly, inactivation of the gene encoding either the C. elegans apoptosis-inducing factor (AIF) homologue (WAH-1), a mitochondrial apoptogenic factor, or the C. elegans phospholipid scramblase 1 (SCRM-1), a plasma membrane protein, reduces phosphatidylserine exposure on the surface of apoptotic germ cells and compromises cell-corpse engulfment. WAH-1 associates with SCRM-1 and activates its phospholipid scrambling activity in vitro. Thus WAH-1, after its release from mitochondria during apoptosis, promotes plasma membrane phosphatidylserine externalization through its downstream effector, SCRM-1.
磷脂酰丝氨酸通常局限于质膜的内小叶，其外化是哺乳动物细胞凋亡的一个标志。目前尚不清楚是什么激活并介导了凋亡细胞中磷脂酰丝氨酸的外化过程。在此，我们报告了一种基于膜联蛋白V的磷脂酰丝氨酸标记方法的开发，并表明秀丽隐杆线虫中的大多数凋亡生殖细胞都有表面暴露的磷脂酰丝氨酸，这表明磷脂酰丝氨酸外化是线虫中保守的凋亡事件。重要的是，编码秀丽隐杆线虫凋亡诱导因子（AIF）同源物（WAH-1，一种线粒体凋亡因子）或秀丽隐杆线虫磷脂翻转酶1（SCRM-1，一种质膜蛋白）的基因失活，会减少凋亡生殖细胞表面的磷脂酰丝氨酸暴露，并损害细胞尸体的吞噬。WAH-1与SCRM-1结合，并在体外激活其磷脂翻转活性。因此，WAH-1在凋亡过程中从线粒体释放后，通过其下游效应物SCRM-1促进质膜磷脂酰丝氨酸的外化。
