Cell corpse engulfment mediated by C. elegans phosphatidylserine receptor through CED-5 and CED-12.
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
Xiaochen
X
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.
Wu
Yi-Chun
YC
Fadok
Valerie A
VA
Lee
Ming-Chia
MC
Gengyo-Ando
Keiko
K
Cheng
Li-Chun
LC
Ledwich
Duncan
D
Hsu
Pei-Ken
PK
Chen
Jia-Yun
JY
Chou
Bin-Kuan
BK
Henson
Peter
P
Mitani
Shohei
S
Xue
Ding
D
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
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