C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells through phospholipid scramblase SCRM-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.
Wang
Xiaochen
X
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Wang
Jin
J
Gengyo-Ando
Keiko
K
Gu
Lichuan
L
Sun
Chun-Ling
CL
Yang
Chonglin
C
Shi
Yong
Y
Kobayashi
Tetsuo
T
Shi
Yigong
Y
Mitani
Shohei
S
Xie
Xiao-Song
XS
Xue
Ding
D
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D001692:Biological Transport; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D005854:Germ Cells / Q000201:enzymology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors
D017304:Annexin A5; C479695:CED-2 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; C520307:SCRM-1 protein, C elegans; C469543:Wah-1 protein, C elegans; C422043:ced-1 protein, C elegans; D020169:Caspases; C089223:ced-3 protein, C elegans