title: Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12.
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.
authors.affiliation: Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Wang
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Wu
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Fadok
authors.forename: Ming-Chia
authors.initials: MC
authors.lastname: Lee
authors.forename: Keiko
authors.initials: K
authors.lastname: Gengyo-Ando
authors.forename: Li-Chun
authors.initials: LC
authors.lastname: Cheng
authors.forename: Duncan
authors.initials: D
authors.lastname: Ledwich
authors.forename: Pei-Ken
authors.initials: PK
authors.lastname: Hsu
authors.forename: Jia-Yun
authors.initials: JY
authors.lastname: Chen
authors.forename: Bin-Kuan
authors.initials: BK
authors.lastname: Chou
authors.forename: Peter
authors.initials: P
authors.lastname: Henson
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.forename: Ding
authors.initials: D
authors.lastname: Xue
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D047108:Embryonic Development; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C407268:CED-10 protein, C elegans; C438369:CED-12 protein, C elegans; C479695:CED-2 protein, C elegans; C111579:CED-5 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C486678:ELMO2 protein, human; C486679:ELMO3 protein, human; D008565:Membrane Proteins; D010718:Phosphatidylserines; C479694:Psr-1 protein, C elegans; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C408123:phosphatidylserine receptor; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; D020744:rac GTP-Binding Proteins