Caspase-mediated activation of Caenorhabditis elegans CED-8 promotes apoptosis and phosphatidylserine externalization.
During apoptosis, phosphatidylserine (PS), normally restricted to the inner leaflet of the plasma membrane, is exposed on the surface of apoptotic cells and serves as an 'eat-me' signal to trigger phagocytosis. It is poorly understood how PS exposure is activated in apoptotic cells. Here we report that CED-8, a Caenorhabditis elegans protein implicated in controlling the kinetics of apoptosis and a homologue of the XK family proteins, is a substrate of the CED-3 caspase. Cleavage of CED-8 by CED-3 activates its proapoptotic function and generates a carboxyl-terminal cleavage product, acCED-8, that promotes PS externalization in apoptotic cells and can induce ectopic PS exposure in living cells. Consistent with its role in promoting PS externalization in apoptotic cells, ced-8 is important for cell corpse engulfment in C. elegans. Our finding identifies a crucial link between caspase activation and PS externalization, which triggers phagocytosis of apoptotic cells.
1] Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA [2] Division of Biochemistry and Cellular Molecular Biology, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan 333, China [3].
Yu-Zen
YZ
Chen
James
J
Mapes
Eui-Seung
ES
Lee
Riley Robert
RR
Skeen-Gaar
Ding
D
Xue
D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism*
C410597:CED-8 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D010718:Phosphatidylserines; D049452:Green Fluorescent Proteins; D020169:Caspases; C089223:ced-3 protein, C elegans