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

@article{Wang2003CellCE,
  title={Cell Corpse Engulfment Mediated by C. elegans Phosphatidylserine Receptor Through CED-5 and CED-12},
  author={Xiaochen Wang and Yi-Chun Wu and Valerie Fadok and Ming-Chia Lee and Keiko Gengyo-Ando and Li-chun Cheng and Duncan Ledwich and Pei-Ken Hsu and Jia-Yun Chen and Bin-Kuan Chou and Peter M. Henson and Shohei Mitani and Ding Xue},
  journal={Science},
  year={2003},
  volume={302},
  pages={1563 - 1566}
}
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… Expand
Caspase-mediated activation of Caenorhabditis elegans CED-8 promotes apoptosis and phosphatidylserine externalisation
TLDR
CED-8, a C. elegans protein implicated in controlling the kinetics of apoptosis and a homolog of the XK family proteins, is a substrate of the CED-3 caspase that generates a carboxyl terminal cleavage product that promotes PS externalization in apoptotic cells and can induce ectopic PS exposure in living cells. Expand
Two alternative mechanisms that regulate the presentation of apoptotic cell engulfment signal in Caenorhabditis elegans.
TLDR
Observations suggest that phosphatidylserine might be recognized by CED-1 and act as a conserved eat-me signal from nematodes to mammals, and the two different biochemical activities used in somatic cells (ABC transporter) and germ cells (phospholipid scramblase) suggest an increased complexity in the regulation of phosphatidoserine presentation in response to apoptotic signals in different tissues and during different developmental stages. Expand
C. elegans transthyretin-like protein TTR-52 mediates recognition of apoptotic cells by the CED-1 phagocyte receptor
TLDR
TTR-52 is the first bridging molecule identified in C. elegans that mediates recognition of apoptotic cells by crosslinking the PtdSer 'eat me' signal with the phagocyte receptor CED-1. Expand
Engulfment of Apoptotic Cells in C. elegans Is Mediated by Integrin α/SRC Signaling
TLDR
Evidence is provided that integrin functions as an engulfment receptor at the whole-organism level and a nonconventional signaling pathway in which SRC provides a FAK-independent linkage between integrin alpha and the common motility-promoting signaling module CED-2/CrkII-CED-5/Dock180-Ced-12/ELMO to promote the internalization of apoptotic cells is revealed. Expand
A lysine-rich motif in the phosphatidylserine receptor PSR-1 mediates recognition and removal of apoptotic cells
TLDR
A lysine-rich motif in the extracellular domain of PSR-1, the Caenorhabditis elegans PSR, mediates specific phosphatidylserine binding in vitro and clearance of apoptotic cells in vivo, suggesting a mechanism by which PSr-1 activates phagocytosis. Expand
CED-1, CED-7, and TTR-52 Regulate Surface Phosphatidylserine Expression on Apoptotic and Phagocytic Cells
TLDR
CED-7 and Ttr-52 may promote the efflux of PS from apoptotic cells through the generation of extracellular PS vesicles, which lead to exPS expression on phagocytes via TTR-52 and CED-1 to facilitate cell corpse clearance. Expand
The Drosophila homolog of the putative phosphatidylserine receptor functions to inhibit apoptosis
TLDR
Exposure of phosphatidylserine is a conserved feature of apoptotic cells and is thought to act as a signal for engulfment of the cell corpse, but it is surprised to find that overexpression of d PSR protects from apoptosis, while loss of dPSR enhances apoptosis in the developing eye. Expand
Structural study of TTR-52 reveals the mechanism by which a bridging molecule mediates apoptotic cell engulfment.
TLDR
The structural and functional studies of Caenorhabditis elegans TTR-52, a recently identified bridging molecule that cross-links surface-exposed phosphatidylserine (PtdSer) on apoptotic cells to the CED-1 receptor on phagocytes, reveal the first full-length structure of a bridging substance and the mechanism underlying bridging molecules-mediated apoptotic cell recognition. Expand
Aminophospholipid Translocase TAT-1 Promotes Phosphatidylserine Exposure during C. elegans Apoptosis
TLDR
It is shown that PS exposure can readily be detected on apoptotic C. elegans cells, and it is proposed that tat-1 homologs might also play an important role in PS exposure in mammals. Expand
C. elegans Secreted Lipid-Binding Protein NRF-5 Mediates PS Appearance on Phagocytes for Cell Corpse Engulfment
TLDR
The 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. Expand
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References

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CED-1 Is a Transmembrane Receptor that Mediates Cell Corpse Engulfment in C. elegans
TLDR
The results indicate that CED-1 is a cell surface phagocytic receptor that recognizes cell corpses, and suggests that the ABC transporter C ED-7 promotes cell corpse recognition by Ced-1, possibly by exposing a phospholipid ligand on the surfaces of cell corpses. Expand
A receptor for phosphatidylserine-specific clearance of apoptotic cells
TLDR
Using phage display, a gene that appears to recognize phosphatidylserine on apoptotic cells is cloned and shown to be highly homologous to genes of unknown function in Caenorhabditis elegans and Drosophila melanogaster, suggesting that phosphatido-serine recognition on apoptosis cells during their removal by phagocytes is highly conserved throughout phylogeny. Expand
C. elegans phagocytosis and cell-migration protein CED-5 is similar to human DOCK180
TLDR
This work reports that ced-5, a gene required for cell-corpse engulfment in the nematode Caenorhabditis elegans, encodes a protein that is similar to the human protein DOCK180 and the Drosophila melanogaster protein Myoblast City, both of which have been implicated in the extension of cell surfaces. Expand
Phosphatidylserine (PS) induces PS receptor–mediated macropinocytosis and promotes clearance of apoptotic cells
TLDR
The results suggest that regardless of the receptors engaged on the phagocyte, ingestion does not occur in the absence of phosphatidylserine (PS), and recognition of PS was found to be dependent on the presence of the PS receptor (PSR). Expand
CED-2/CrkII and CED-10/Rac control phagocytosis and cell migration in Caenorhabditis elegans
TLDR
It is proposed that CED-2/CrkII and Ced-5/DOCK180 function to activate CED -10/Rac in a GTPase signalling pathway that controls the polarized extension of cell surfaces. Expand
C. elegans CED-12 acts in the conserved crkII/DOCK180/Rac pathway to control cell migration and cell corpse engulfment.
TLDR
It is suggested that CED-12 counterparts in higher organisms regulate cytoskeleton dynamics, as Ced-12 does in C. elegans, by the formation and localization of a C ED-2-CED-5-C ED-12 ternary complex to the plasma membrane, leading to the cytoskeletal reorganization that occurs in the polarized extension of cell surfaces in engulfing cells and migrating cells. Expand
Genes required for the engulfment of cell corpses during programmed cell death in Caenorhabditis elegans.
TLDR
Five new genes are identified that play a role in eliminating cell corpses in the nematode Caenorhabditis elegans and electron microscopic studies reveal that mutations in each of these genes prevent engulfment, indicating that these genes are needed either for the recognition of corpses by other cells or for the initiation of phagocytosis. Expand
CED-12/ELMO, a Novel Member of the CrkII/Dock180/Rac Pathway, Is Required for Phagocytosis and Cell Migration
TLDR
These studies identify CED-12/ELMO as an upstream regulator of Rac1 that affects engulfment and cell migration from C. elegans to mammals. Expand
Loss of Phospholipid Asymmetry and Surface Exposure of Phosphatidylserine Is Required for Phagocytosis of Apoptotic Cells by Macrophages and Fibroblasts*
TLDR
Observations directly demonstrate that loss of phospholipid asymmetry and PS expression is required for phagocyte engulfment of apoptotic cells and imply a critical, if not obligatory, role for PS recognition in the uptake process. Expand
Essential role of phosphatidylserine externalization in apoptosing cell phagocytosis by macrophages.
TLDR
It is suggested that PS is externalized as a result of membrane phospholipid redistribution and externalized PS by itself induces apoptosing cell phagocytosis. Expand
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