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

Author:

Wang Xiaochen1234,Wu Yi-Chun1234,Fadok Valerie A.1234,Lee Ming-Chia1234,Gengyo-Ando Keiko1234,Cheng Li-Chun1234,Ledwich Duncan1234,Hsu Pei-Ken1234,Chen Jia-Yun1234,Chou Bin-Kuan1234,Henson Peter1234,Mitani Shohei1234,Xue Ding1234

Affiliation:

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.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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