C. elegans secreted lipid-binding protein NRF-5 mediates PS appearance on phagocytes for cell corpse engulfment.
BACKGROUND
During programmed cell death, apoptotic cells are rapidly removed by phagocytes. How dying cells are recognized remains poorly understood.


RESULTS
Here we identify a secreted lipid transfer/LPS-binding family protein, NRF-5, which is required for efficient clearance of cell corpses. We observed that phosphatidylserine (PS), which is externalized to the outer leaflet of plasma membranes in apoptotic cells, is also detected on the surface of engulfing cells. Loss of NRF-5 function completely blocks PS appearance on engulfing cells but causes accumulation of PS on apoptotic cells, a phenotype observed in both ced-7(lf) and ttr-52(lf) mutants. The NRF-5 protein is expressed in and secreted from body wall muscle cells and clusters around apoptotic cells in a CED-7-dependent manner. NRF-5 associates with TTR-52, binds PS, and displays lipid transfer activity in vitro.


CONCLUSIONS
Our data suggest that NRF-5 may act with CED-7 and TTR-52 to mediate PS transfer from apoptotic cells to engulfing cells and thus promotes engulfment by phagocytes.
Graduate Program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Yan
Y
Zhang
Haibin
H
Wang
Eriko
E
Kage-Nakadai
Shohei
S
Mitani
Xiaochen
X
Wang
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D010586:Phagocytes / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C576460:NRF-5 protein, C elegans; D010718:Phosphatidylserines