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Cell corpse engulfment mediated by C ele ... ceptor through CED-5 and CED-12


Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12.

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During apoptosis, phosphatidylserine, which is normally restricted to the inner leaflet of the plasma membrane, is exposed on the surface of apoptotic cells and has been suggested to act as an eat-me signal to trigger phagocytosis. It is unclear how phagocytes recognize phosphatidylserine. Recently, a putative phosphatidylserine receptor (PSR) was identified and proposed to mediate recognition of phosphatidylserine and phagocytosis. We report that psr-1, the Caenorhabditis elegans homolog of PSR, is important for cell corpse engulfment. In vitro PSR-1 binds preferentially phosphatidylserine or cells with exposed phosphatidylserine. In C. elegans, PSR-1 acts in the same cell corpse engulfment pathway mediated by intracellular signaling molecules CED-2 (homologous to the human CrkII protein), CED-5 (DOCK180), CED-10 (Rac GTPase), and CED-12 (ELMO), possibly through direct interaction with CED-5 and CED-12. Our findings suggest that PSR-1 is likely an upstream receptor for the signaling pathway containing CED-2, CED-5, CED-10, and CED-12 proteins and plays an important role in recognizing phosphatidylserine during phagocytosis.


Wang X, Wu YC, Fadok VA, Lee MC, Gengyo-Ando K, Cheng LC, Ledwich D, Hsu PK, Chen JY, Chou BK, Henson P, Mitani S, Xue D

Science (New York, N.Y.)

2003-11-28 00:00

302

5650

1563-6

Adaptor Proteins, Signal Transducing,Amino Acid Sequence,Animals,Apoptosis,Caenorhabditis elegans,Caenorhabditis elegans Proteins,Carrier Proteins,Cytoskeletal Proteins,Embryo, Nonmammalian,Embryonic Development,Humans,Membrane Proteins,Molecular Sequence Data,Mutation,Phagocytosis,Phosphatidylserines,Protein Binding,Receptors, Cell Surface,Recombinant Fusion Proteins,Recombinant Proteins,Signal Transduction,rac GTP-Binding Proteins,Adaptor Proteins, Signal Transducing,CED-10 protein, C elegans,CED-12 protein, C elegans,CED-2 protein, C elegans,CED-5 protein, C elegans,Caenorhabditis elegans Proteins,Carrier Proteins,Cytoskeletal Proteins,ELMO2 protein, human,ELMO3 protein, human,Membrane Proteins,PTDSR protein, human,Phosphatidylserines,Psr-1 protein, C elegans,Receptors, Cell Surface,Recombinant Fusion Proteins,Recombinant Proteins,phosphatidylserine receptor,rac GTP-Binding Proteins

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA

Science


1095-9203

10.1126/science.1087641

302/5650/1563

1358

True

14645848

Ding Xue
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