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Science 28 November 2003:
Vol. 302. no. 5650, pp. 1563 - 1566
DOI: 10.1126/science.1087641
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Reports

Cell Corpse Engulfment Mediated by C. elegans Phosphatidylserine Receptor Through CED-5 and CED-12

Xiaochen Wang,1* Yi-Chun Wu,2*{dagger} Valerie A. Fadok,3 Ming-Chia Lee,2 Keiko Gengyo-Ando,4 Li-Chun Cheng,2 Duncan Ledwich,1 Pei-Ken Hsu,2 Jia-Yun Chen,2 Bin-Kuan Chou,2 Peter Henson,3 Shohei Mitani,4 Ding Xue1{dagger}

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.

1 Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
2 Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan 10617.
3 Program in Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
4 Department of Physiology, Tokyo Women's Medical University, School of Medicine, Tokyo, 162-8666, Japan.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: ding.xue{at}colorado.edu, yichun{at}ntu.edu.tw

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