Letter abstract
Nature Cell Biology 9, 541 - 549 (2007)
Published online: 1 April 2007 | doi:10.1038/ncb1574
C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-1
Xiaochen Wang1,5, Jin Wang2, Keiko Gengyo-Ando3, Lichuan Gu4, Chun-Ling Sun1, Chonglin Yang1, Yong Shi1, Tetsuo Kobayashi3, Yigong Shi4, Shohei Mitani3, Xiao-Song Xie2 & Ding Xue1
Externalization of phosphatidylserine, which is normally restricted to the inner leaflet of plasma membrane, is a hallmark of mammalian apoptosis1, 2, 3, 4. 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)5, 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.
- Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
- McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
- Department of Physiology, Tokyo Women's Medical University, School of Medicine, and CREST, JST, Tokyo, 162-8666, Japan.
- Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
- Current address: National Institute of Biological Sciences, Beijing, 102206, China.
Correspondence to: Ding Xue1 e-mail: ding.xue@colorado.edu
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