ced-1

UniProt ID: Q9XWD6
Organism: Caenorhabditis elegans
Review Status: COMPLETE
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Gene Description

CED-1 is the C. elegans engulfment receptor for apoptotic cell corpses, a single-pass transmembrane protein of the CED-1/Draper/MEGF10 family with an EMI domain, extracellular EGF-like repeats and a cytoplasmic tail carrying NPXY and YXXL motifs. Expressed on engulfing cells, it clusters around neighbouring corpses and recognizes them through the secreted bridging protein TTR-52, which binds exposed phosphatidylserine. Its NPXY motif recruits the PTB-domain adaptor CED-6/GULP and, with the ABC transporter CED-7 and dynamin DYN-1, it drives pseudopod extension, actin reorganization and internalization, then initiates phagosome maturation through PI(3)P and RAB-7. After engulfment it is recycled to the plasma membrane by retromer. Engulfing cells also use it to promote the death of cells that receive weak death signals, and it contributes to defense against bacterial pathogens.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000132 establishment of mitotic spindle orientation
IGI
PMID:20126385
The Wnt pathway controls cell death engulfment, spindle orie...
MARK AS OVER ANNOTATED
Summary: Establishment of mitotic spindle orientation (IGI with mom-5, Cabello et al. 2010).
Reason: In the full text, spindle orientation needs MOM-5/Frizzled, GSK-3 and beta-catenins. Spindle defects appear only in a small fraction of ced-1; ced-5 double mutants, and the authors write that they 'cannot exclude' a role. This does not show that CED-1 orients spindles.
Supporting Evidence:
PMID:20126385
we did observe spindle defects in a small fraction of ced-1; ced-5 double mutants
GO:0001845 phagolysosome assembly
IMP
PMID:18351800
Phagocytic receptor CED-1 initiates a signaling pathway for ...
ACCEPT
Summary: CED-1 initiates phagosome maturation and phagolysosome formation (Yu et al. 2008).
Reason: IMP with full text. The CED-1/CED-6/DYN-1 pathway sets the rate of PI(3)P and RAB-7 enrichment on phagosomes and the formation of phagolysosomes. The receptor that initiates engulfment also drives degradation of the engulfed corpse.
Supporting Evidence:
PMID:18351800
One of the pathways, composed of CED-1, the adaptor protein CED-6, and DYN-1, controls the rate of enrichment of PI(3)P and RAB-7 on phagosomal surfaces and the formation of phagolysosomes
GO:0001891 phagocytic cup
IDA
PMID:20133524
Retromer is required for apoptotic cell clearance by phagocy...
ACCEPT
Summary: CED-1 at the phagocytic cup (IDA, Chen et al. 2010).
Reason: The cached record is abstract-only. CED-1::GFP marks budding pseudopods and phagocytic cups in time-lapse imaging, so the location is well established.
Supporting Evidence:
PMID:18351800
the CED-1::GFP signal rapidly disappeared from phagosomal surface after the enclosure of the phagocytic cup
PMID:11163239
The CED-1 protein localizes to cell membranes and clusters around neighboring cell corpses
GO:0005044 scavenger receptor activity
IBA
GO_REF:0000033
ACCEPT
Summary: Scavenger receptor activity (IBA (PTN009076277, sources MEGF10 and ced-1)).
Reason: CED-1 is the founding member of the CED-1/Draper/MEGF10 scavenger-receptor family. Through its EMI domain it binds the bridging molecule TTR-52, which binds phosphatidylserine on apoptotic cells. Core molecular function.
Supporting Evidence:
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
PMID:20526330
binds to both PtdSer and the extracellular domain of CED-1 in vitro
GO:0005044 scavenger receptor activity
IEA
GO_REF:0000002
ACCEPT
Summary: Scavenger receptor activity (InterPro2GO (MEGF10/SREC1/2-like family)).
Reason: CED-1 is the founding member of the CED-1/Draper/MEGF10 scavenger-receptor family. Through its EMI domain it binds the bridging molecule TTR-52, which binds phosphatidylserine on apoptotic cells. Core molecular function.
Supporting Evidence:
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
PMID:20526330
binds to both PtdSer and the extracellular domain of CED-1 in vitro
GO:0005044 scavenger receptor activity
IPI
PMID:20526330
Caenorhabditis elegans transthyretin-like protein TTR-52 med...
ACCEPT
Summary: CED-1 extracellular domain binds the bridging molecule TTR-52 (IPI, Wang et al. 2010).
Reason: CED-1 is the founding member of the CED-1/Draper/MEGF10 scavenger-receptor family. Through its EMI domain it binds the bridging molecule TTR-52, which binds phosphatidylserine on apoptotic cells. The IPI with TTR-52 is the ligand-recognition step.
Supporting Evidence:
PMID:20526330
binds to both PtdSer and the extracellular domain of CED-1 in vitro
PMID:22713871
CED-1 binds TTR-52 through its N-terminal EMI domain
GO:0005044 scavenger receptor activity
ISS
PMID:11163239
CED-1 is a transmembrane receptor that mediates cell corpse ...
ACCEPT
Summary: Scavenger receptor activity by similarity to SREC (ISS).
Reason: CED-1 is the founding member of the CED-1/Draper/MEGF10 scavenger-receptor family. Through its EMI domain it binds the bridging molecule TTR-52, which binds phosphatidylserine on apoptotic cells.
Supporting Evidence:
PMID:11163239
ced-1 encodes a transmembrane protein similar to human SREC (Scavenger Receptor from Endothelial Cells)
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
GO:0005515 protein binding
IPI
PMID:11729193
Interaction of CED-6/GULP, an adapter protein involved in en...
MODIFY
Summary: CED-1 cytoplasmic NPXY motif binds the PTB domain of CED-6/GULP (Su et al. 2002).
Reason: 'Protein binding' is uninformative. The interaction is how the CED-1 receptor passes its signal to its adaptor, and the intracellular PTB/SH2-binding motifs are needed for engulfment but not for clustering. The informative activity is signaling receptor activity.
Proposed replacements: signaling receptor activity
Supporting Evidence:
PMID:11729193
we present evidence for a physical interaction between GULP/CED-6 and one of the two motifs (NPXY motif) in the cytoplasmic tail of CED-1
PMID:11163239
Motifs in the intracellular domain of CED-1 known to interact with PTB and SH2 domains were necessary for engulfment but not for clustering
GO:0005515 protein binding
IPI
PMID:11729193
Interaction of CED-6/GULP, an adapter protein involved in en...
MODIFY
Summary: CED-1 cytoplasmic NPXY motif binds the PTB domain of CED-6/GULP (Su et al. 2002).
Reason: 'Protein binding' is uninformative. The interaction is how the CED-1 receptor passes its signal to its adaptor, and the intracellular PTB/SH2-binding motifs are needed for engulfment but not for clustering. The informative activity is signaling receptor activity.
Proposed replacements: signaling receptor activity
Supporting Evidence:
PMID:11729193
we present evidence for a physical interaction between GULP/CED-6 and one of the two motifs (NPXY motif) in the cytoplasmic tail of CED-1
PMID:11163239
Motifs in the intracellular domain of CED-1 known to interact with PTB and SH2 domains were necessary for engulfment but not for clustering
GO:0005515 protein binding
IPI
PMID:22713871
Structural study of TTR-52 reveals the mechanism by which a ...
MODIFY
Summary: CED-1 EMI domain binds TTR-52 (Kang et al. 2012).
Reason: 'Protein binding' is uninformative. The binding partner is a phosphatidylserine-bridging ligand, so the interaction is the receptor's ligand-recognition activity, captured by scavenger receptor activity.
Proposed replacements: scavenger receptor activity
Supporting Evidence:
PMID:22713871
CED-1 binds TTR-52 through its N-terminal EMI domain
PMID:20526330
binds to both PtdSer and the extracellular domain of CED-1 in vitro
GO:0005886 plasma membrane
EXP
PMID:35929733
trim-21 promotes proteasomal degradation of CED-1 for apopto...
ACCEPT
Summary: Plasma membrane.
Reason: CED-1 is a single-pass transmembrane receptor at the engulfing-cell surface and is recycled back to the plasma membrane from phagosomes.
Supporting Evidence:
PMID:11163239
The CED-1 protein localizes to cell membranes and clusters around neighboring cell corpses
PMID:35929733
CED-1 is recycled from phagosome membranes to plasma membranes via the retromer complex
GO:0005886 plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: Plasma membrane.
Reason: CED-1 is a single-pass transmembrane receptor at the engulfing-cell surface and is recycled back to the plasma membrane from phagosomes.
Supporting Evidence:
PMID:11163239
The CED-1 protein localizes to cell membranes and clusters around neighboring cell corpses
PMID:35929733
CED-1 is recycled from phagosome membranes to plasma membranes via the retromer complex
GO:0005886 plasma membrane
IDA
PMID:11163239
CED-1 is a transmembrane receptor that mediates cell corpse ...
ACCEPT
Summary: Plasma membrane.
Reason: CED-1 is a single-pass transmembrane receptor at the engulfing-cell surface and is recycled back to the plasma membrane from phagosomes.
Supporting Evidence:
PMID:11163239
The CED-1 protein localizes to cell membranes and clusters around neighboring cell corpses
PMID:35929733
CED-1 is recycled from phagosome membranes to plasma membranes via the retromer complex
GO:0005886 plasma membrane
IDA
PMID:20133524
Retromer is required for apoptotic cell clearance by phagocy...
ACCEPT
Summary: Plasma membrane.
Reason: CED-1 is a single-pass transmembrane receptor at the engulfing-cell surface and is recycled back to the plasma membrane from phagosomes.
Supporting Evidence:
PMID:11163239
The CED-1 protein localizes to cell membranes and clusters around neighboring cell corpses
PMID:35929733
CED-1 is recycled from phagosome membranes to plasma membranes via the retromer complex
GO:0005886 plasma membrane
IEA
GO_REF:0000044
ACCEPT
Summary: Plasma membrane.
Reason: CED-1 is a single-pass transmembrane receptor at the engulfing-cell surface and is recycled back to the plasma membrane from phagosomes.
Supporting Evidence:
PMID:11163239
The CED-1 protein localizes to cell membranes and clusters around neighboring cell corpses
PMID:35929733
CED-1 is recycled from phagosome membranes to plasma membranes via the retromer complex
GO:0009986 cell surface
IDA
PMID:11163239
CED-1 is a transmembrane receptor that mediates cell corpse ...
ACCEPT
Summary: Cell surface (IDA).
Reason: CED-1 is displayed on the engulfing-cell surface, where it clusters around corpses.
Supporting Evidence:
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
PMID:11163239
The CED-1 protein localizes to cell membranes and clusters around neighboring cell corpses
GO:0012501 programmed cell death
IMP
PMID:6857247
Mutations affecting programmed cell deaths in the nematode C...
MARK AS OVER ANNOTATED
Summary: Programmed cell death (IMP, Hedgecock et al. 1983).
Reason: The source paper concludes that cells programmed to die still die in engulfment mutants, so engulfment is not needed for most deaths. Engulfment genes do promote death in sensitized backgrounds (Reddien et al. 2001), but that is a regulatory role, captured here by positive regulation of apoptotic process involved in development. CED-1 is not part of the death program itself.
Supporting Evidence:
PMID:6857247
With few exceptions, these cells still die, suggesting that, in nematodes, engulfment is not necessary for most programmed deaths
PMID:11449278
the expression in engulfing cells of ced-1, which encodes a receptor that recognizes cell corpses, rescues the cell-killing defects of ced-1 mutants
GO:0016192 vesicle-mediated transport
IEA
GO_REF:0000108
MARK AS OVER ANNOTATED
Summary: Vesicle-mediated transport (inferred from scavenger receptor activity).
Reason: Correct but uninformative parent of receptor-mediated engulfment. Engulfment of apoptotic cell is already annotated.
Supporting Evidence:
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
GO:0030036 actin cytoskeleton organization
IDA
PMID:15744306
Two pathways converge at CED-10 to mediate actin rearrangeme...
KEEP AS NON CORE
Summary: Actin reorganization around corpses requires CED-1 (Kinchen et al. 2005).
Reason: IDA. Actin rearrangement around the corpse is a step within engulfment and is downstream of CED-1 signaling, so it is kept as a non-core component of the engulfment role.
Supporting Evidence:
PMID:15744306
CED-1, CED-6 and CED-7 are required for actin reorganization around the apoptotic cell corpse
GO:0030670 phagocytic vesicle membrane
IDA
PMID:16740477
C. elegans Dynamin mediates the signaling of phagocytic rece...
ACCEPT
Summary: CED-1 on the phagosome membrane (IDA, Yu et al. 2006).
Reason: The cached record is abstract-only. Time-lapse imaging shows CED-1::GFP on the nascent phagosome surface, from which it is then recycled.
Supporting Evidence:
PMID:18351800
the CED-1::GFP signal rapidly disappeared from phagosomal surface after the enclosure of the phagocytic cup
PMID:35929733
CED-1 is recycled from phagosome membranes to plasma membranes via the retromer complex
GO:0030670 phagocytic vesicle membrane
IEA
GO_REF:0000044
ACCEPT
Summary: Phagocytic vesicle membrane (electronic).
Reason: Consistent with the experimental data.
Supporting Evidence:
PMID:18351800
the CED-1::GFP signal rapidly disappeared from phagosomal surface after the enclosure of the phagocytic cup
GO:0031260 pseudopodium membrane
IDA
PMID:16740477
C. elegans Dynamin mediates the signaling of phagocytic rece...
ACCEPT
Summary: CED-1 on extending pseudopods around corpses.
Reason: CED-1 clusters on the engulfing-cell membrane around corpses, including the pseudopods that wrap them.
Supporting Evidence:
PMID:11163239
The CED-1 protein localizes to cell membranes and clusters around neighboring cell corpses
PMID:16740477
DYN-1 transiently accumulates to the surface of pseudopods in a manner dependent on ced-1, ced-6, and ced-7
GO:0031260 pseudopodium membrane
IDA
PMID:21148288
Three sorting nexins drive the degradation of apoptotic cell...
ACCEPT
Summary: CED-1 on extending pseudopods around corpses.
Reason: CED-1 clusters on the engulfing-cell membrane around corpses, including the pseudopods that wrap them.
Supporting Evidence:
PMID:11163239
The CED-1 protein localizes to cell membranes and clusters around neighboring cell corpses
PMID:16740477
DYN-1 transiently accumulates to the surface of pseudopods in a manner dependent on ced-1, ced-6, and ced-7
GO:0034620 cellular response to unfolded protein
IDA
PMID:18606143
Unfolded protein response genes regulated by CED-1 are requi...
MARK AS OVER ANNOTATED
Summary: Cellular response to unfolded protein (IDA, Haskins et al. 2008).
Reason: CED-1 is needed for expression of pqn/abu genes, which the authors class as a noncanonical unfolded protein response during infection. No study shows CED-1 responding to unfolded protein. The finding is about immune gene expression and is covered by defense response to bacterium.
Supporting Evidence:
PMID:18606143
CED-1 functions to activate the expression of pqn/abu genes
GO:0042742 defense response to bacterium
IMP
PMID:18606143
Unfolded protein response genes regulated by CED-1 are requi...
KEEP AS NON CORE
Summary: ced-1 mutants are killed faster by Salmonella (Haskins et al. 2008).
Reason: IMP with full text. This is a real but secondary role of CED-1 in innate immunity, separate from its engulfment function.
Supporting Evidence:
PMID:18606143
loss-of-function ced-1 mutants are immunocompromised animals and are rapidly killed by live bacteria
PMID:18606143
CED-1 functions to activate the expression of pqn/abu genes
GO:0043652 engulfment of apoptotic cell
IBA
GO_REF:0000033
ACCEPT
Summary: Engulfment of apoptotic cell.
Reason: CED-1 is the engulfing-cell receptor of the CED-1/CED-6/CED-7 corpse-clearance pathway: it recognizes cell corpses, signals through CED-6 and DYN-1, and initiates phagosome maturation. Core process.
Supporting Evidence:
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
PMID:11449278
the expression in engulfing cells of ced-1, which encodes a receptor that recognizes cell corpses, rescues the cell-killing defects of ced-1 mutants
GO:0043652 engulfment of apoptotic cell
IDA
PMID:11163239
CED-1 is a transmembrane receptor that mediates cell corpse ...
ACCEPT
Summary: Engulfment of apoptotic cell.
Reason: CED-1 is the engulfing-cell receptor of the CED-1/CED-6/CED-7 corpse-clearance pathway: it recognizes cell corpses, signals through CED-6 and DYN-1, and initiates phagosome maturation. Core process.
Supporting Evidence:
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
PMID:11163239
ced-1 is expressed in and functions in engulfing cells
GO:0043652 engulfment of apoptotic cell
IDA
PMID:15744306
Two pathways converge at CED-10 to mediate actin rearrangeme...
ACCEPT
Summary: Engulfment of apoptotic cell.
Reason: CED-1 is the engulfing-cell receptor of the CED-1/CED-6/CED-7 corpse-clearance pathway: it recognizes cell corpses, signals through CED-6 and DYN-1, and initiates phagosome maturation. Core process.
Supporting Evidence:
PMID:15744306
CED-1, CED-6 and CED-7 are required for actin reorganization around the apoptotic cell corpse
GO:0043652 engulfment of apoptotic cell
IMP
PMID:11163239
CED-1 is a transmembrane receptor that mediates cell corpse ...
ACCEPT
Summary: Engulfment of apoptotic cell.
Reason: CED-1 is the engulfing-cell receptor of the CED-1/CED-6/CED-7 corpse-clearance pathway: it recognizes cell corpses, signals through CED-6 and DYN-1, and initiates phagosome maturation. Core process.
Supporting Evidence:
PMID:11163239
ced-1 is expressed in and functions in engulfing cells
PMID:1936965
mutations in each of these genes prevent engulfment
GO:0043652 engulfment of apoptotic cell
IMP
PMID:18351800
Phagocytic receptor CED-1 initiates a signaling pathway for ...
ACCEPT
Summary: Engulfment of apoptotic cell.
Reason: CED-1 is the engulfing-cell receptor of the CED-1/CED-6/CED-7 corpse-clearance pathway: it recognizes cell corpses, signals through CED-6 and DYN-1, and initiates phagosome maturation. Core process.
Supporting Evidence:
PMID:18351800
One of the pathways, composed of CED-1, the adaptor protein CED-6, and DYN-1, controls the rate of enrichment of PI(3)P and RAB-7 on phagosomal surfaces and the formation of phagolysosomes
GO:0043652 engulfment of apoptotic cell
IMP
PMID:1936965
Genes required for the engulfment of cell corpses during pro...
ACCEPT
Summary: Engulfment of apoptotic cell.
Reason: CED-1 is the engulfing-cell receptor of the CED-1/CED-6/CED-7 corpse-clearance pathway: it recognizes cell corpses, signals through CED-6 and DYN-1, and initiates phagosome maturation. Core process.
Supporting Evidence:
PMID:1936965
mutations in each of these genes prevent engulfment
GO:0043652 engulfment of apoptotic cell
IMP
PMID:19461656
An essential role for calcium flux in phagocytes for apoptot...
ACCEPT
Summary: Engulfment of apoptotic cell.
Reason: CED-1 is the engulfing-cell receptor of the CED-1/CED-6/CED-7 corpse-clearance pathway: it recognizes cell corpses, signals through CED-6 and DYN-1, and initiates phagosome maturation. Core process.
Supporting Evidence:
PMID:19461656
This result was quite comparable to the phenotype seen with knockdown of ced-1
GO:0043654 recognition of apoptotic cell
IDA
PMID:11163239
CED-1 is a transmembrane receptor that mediates cell corpse ...
ACCEPT
Summary: Recognition of apoptotic cell (IDA, Zhou et al. 2001).
Reason: CED-1 recognizes cell corpses as the phagocytic receptor of the CED-1 pathway.
Supporting Evidence:
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
PMID:11163239
The CED-1 protein localizes to cell membranes and clusters around neighboring cell corpses
GO:0045184 establishment of protein localization
IDA
PMID:16740477
C. elegans Dynamin mediates the signaling of phagocytic rece...
MARK AS OVER ANNOTATED
Summary: Establishment of protein localization (IDA, Yu et al. 2006).
Reason: The observation is that DYN-1 recruitment to pseudopods depends on CED-1. That is a downstream step of CED-1 signaling within engulfment, not a protein-localization function of CED-1. The term is too generic to be informative.
Supporting Evidence:
PMID:16740477
DYN-1 transiently accumulates to the surface of pseudopods in a manner dependent on ced-1, ced-6, and ced-7
GO:0070986 left/right axis specification
IGI
PMID:20126385
The Wnt pathway controls cell death engulfment, spindle orie...
MARK AS OVER ANNOTATED
Summary: Left/right axis specification (IGI, Cabello et al. 2010).
Reason: The left/right and spindle phenotypes in this paper depend on MOM-5/Frizzled, GSK-3 and beta-catenins. ced-1 shows at most rare spindle defects in double mutants.
Supporting Evidence:
PMID:20126385
we did observe spindle defects in a small fraction of ced-1; ced-5 double mutants
GO:1901076 positive regulation of engulfment of apoptotic cell
IGI
PMID:20126385
The Wnt pathway controls cell death engulfment, spindle orie...
MODIFY
Summary: Positive regulation of engulfment of apoptotic cell (Cabello et al. 2010).
Reason: CED-1 does not regulate engulfment from outside: it is the receptor that carries it out, and ced-1 single mutants have engulfment defects in this paper. The direct process term is the accurate one.
Proposed replacements: engulfment of apoptotic cell
Supporting Evidence:
PMID:20126385
ced-1, ced-7, or ced-6 single mutants showed a weaker engulfment defect
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
GO:1901076 positive regulation of engulfment of apoptotic cell
IGI
PMID:20126385
The Wnt pathway controls cell death engulfment, spindle orie...
MODIFY
Summary: Positive regulation of engulfment of apoptotic cell (Cabello et al. 2010).
Reason: CED-1 does not regulate engulfment from outside: it is the receptor that carries it out, and ced-1 single mutants have engulfment defects in this paper. The direct process term is the accurate one.
Proposed replacements: engulfment of apoptotic cell
Supporting Evidence:
PMID:20126385
ced-1, ced-7, or ced-6 single mutants showed a weaker engulfment defect
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
GO:1901076 positive regulation of engulfment of apoptotic cell
IGI
PMID:20126385
The Wnt pathway controls cell death engulfment, spindle orie...
MODIFY
Summary: Positive regulation of engulfment of apoptotic cell (Cabello et al. 2010).
Reason: CED-1 does not regulate engulfment from outside: it is the receptor that carries it out, and ced-1 single mutants have engulfment defects in this paper. The direct process term is the accurate one.
Proposed replacements: engulfment of apoptotic cell
Supporting Evidence:
PMID:20126385
ced-1, ced-7, or ced-6 single mutants showed a weaker engulfment defect
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
GO:1901076 positive regulation of engulfment of apoptotic cell
IMP
PMID:20126385
The Wnt pathway controls cell death engulfment, spindle orie...
MODIFY
Summary: Positive regulation of engulfment of apoptotic cell (Cabello et al. 2010).
Reason: CED-1 does not regulate engulfment from outside: it is the receptor that carries it out, and ced-1 single mutants have engulfment defects in this paper. The direct process term is the accurate one.
Proposed replacements: engulfment of apoptotic cell
Supporting Evidence:
PMID:20126385
ced-1, ced-7, or ced-6 single mutants showed a weaker engulfment defect
PMID:11163239
CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
GO:1902742 apoptotic process involved in development
IGI
PMID:24225442
Caspase-mediated activation of Caenorhabditis elegans CED-8 ...
MODIFY
Summary: Apoptotic process involved in development (Chen et al. 2013, CED-8 paper).
Reason: In the full text, ced-1(e1735) is used as a background that blocks engulfment so that corpses persist and can be counted; the paper tests ced-8, not ced-1. Separately, engulfment genes including ced-1 promote cell death when killing is weakened (Reddien 2001; Hoeppner 2001), and ced-1 expressed in engulfing cells rescues that. CED-1 therefore promotes death from the engulfing cell rather than taking part in the dying cell's apoptotic program. The replacement is GO:0043065 positive regulation of apoptotic process, without the developmental context of its precomposed child GO:1904747.
Context of precomposed term: context dropped
The replacement is unfolded from GO:1904747 positive regulation of apoptotic process involved in development to GO:0043065 (projects/INVOLVED_IN_PRECOMPOSITION.md, round 6); the sign correction (regulation, not participation) is unchanged. The developmental context is not carried: it is where the engulfment genes' pro-death role was measured (Reddien 2001; Hoeppner 2001), not a mechanism, and the role is non-core for this gene.
Supporting Evidence:
PMID:24225442
ced-1(e1735) blocks cell corpse engulfment and sensitizes
PMID:11449278
mutations in engulfment genes alone allow the survival and differentiation of some cells that would normally die
PMID:11449278
the expression in engulfing cells of ced-1, which encodes a receptor that recognizes cell corpses, rescues the cell-killing defects of ced-1 mutants
PMID:11449279
genes that mediate corpse removal can also function to actively kill cells
GO:1902742 apoptotic process involved in development
IMP
PMID:24225442
Caspase-mediated activation of Caenorhabditis elegans CED-8 ...
MODIFY
Summary: Apoptotic process involved in development (Chen et al. 2013, CED-8 paper).
Reason: In the full text, ced-1(e1735) is used as a background that blocks engulfment so that corpses persist and can be counted; the paper tests ced-8, not ced-1. Separately, engulfment genes including ced-1 promote cell death when killing is weakened (Reddien 2001; Hoeppner 2001), and ced-1 expressed in engulfing cells rescues that. CED-1 therefore promotes death from the engulfing cell rather than taking part in the dying cell's apoptotic program. The replacement is GO:0043065 positive regulation of apoptotic process, without the developmental context of its precomposed child GO:1904747.
Context of precomposed term: context dropped
The replacement is unfolded from GO:1904747 positive regulation of apoptotic process involved in development to GO:0043065 (projects/INVOLVED_IN_PRECOMPOSITION.md, round 6); the sign correction (regulation, not participation) is unchanged. The developmental context is not carried: it is where the engulfment genes' pro-death role was measured (Reddien 2001; Hoeppner 2001), not a mechanism, and the role is non-core for this gene.
Supporting Evidence:
PMID:24225442
ced-1(e1735) blocks cell corpse engulfment and sensitizes
PMID:11449278
mutations in engulfment genes alone allow the survival and differentiation of some cells that would normally die
PMID:11449278
the expression in engulfing cells of ced-1, which encodes a receptor that recognizes cell corpses, rescues the cell-killing defects of ced-1 mutants
PMID:11449279
genes that mediate corpse removal can also function to actively kill cells
GO:1903356 positive regulation of distal tip cell migration
IGI
PMID:20126385
The Wnt pathway controls cell death engulfment, spindle orie...
MARK AS OVER ANNOTATED
Summary: Positive regulation of distal tip cell migration (Cabello et al. 2010).
Reason: The source paper's own conclusion is that the CED-1/6/7 pathway plays at most a minor role, if any, in distal tip cell migration, which instead depends on the CED-2/5/12 branch.
Supporting Evidence:
PMID:20126385
we found that the CED-1/6/7 pathway appears to play at most a minor role, if any, in this process
GO:1903356 positive regulation of distal tip cell migration
IGI
PMID:20126385
The Wnt pathway controls cell death engulfment, spindle orie...
MARK AS OVER ANNOTATED
Summary: Positive regulation of distal tip cell migration (Cabello et al. 2010).
Reason: The source paper's own conclusion is that the CED-1/6/7 pathway plays at most a minor role, if any, in distal tip cell migration, which instead depends on the CED-2/5/12 branch.
Supporting Evidence:
PMID:20126385
we found that the CED-1/6/7 pathway appears to play at most a minor role, if any, in this process
GO:1903356 positive regulation of distal tip cell migration
IMP
PMID:20126385
The Wnt pathway controls cell death engulfment, spindle orie...
MARK AS OVER ANNOTATED
Summary: Positive regulation of distal tip cell migration (Cabello et al. 2010).
Reason: The source paper's own conclusion is that the CED-1/6/7 pathway plays at most a minor role, if any, in distal tip cell migration, which instead depends on the CED-2/5/12 branch.
Supporting Evidence:
PMID:20126385
we found that the CED-1/6/7 pathway appears to play at most a minor role, if any, in this process
GO:1904747 positive regulation of apoptotic process involved in development
IGI
PMID:23505386
Both the caspase CSP-1 and a caspase-independent pathway pro...
MODIFY
Summary: Positive regulation of apoptotic process involved in development (Denning et al. 2013).
Reason: The cited paper uses ced-1 as a background and attributes the extra corpses to an engulfment defect, so it does not itself show this. The term is still supported elsewhere: engulfment genes, including ced-1 acting in engulfing cells, promote death of cells receiving weak death signals (Reddien 2001; Hoeppner 2001), which the Denning paper also states. The role is non-core, a consequence of the engulfment role. The claim is positive regulation of apoptotic process (GO:0043065); the precomposed term's developmental context is dropped.
Context of precomposed term: context dropped
Decomposed from the precomposed GO:1904747 positive regulation of apoptotic process involved in development (projects/INVOLVED_IN_PRECOMPOSITION.md, round 6), which positively regulates GO:1902742 apoptotic process involved in development, to the regulation genus GO:0043065. The developmental context is not carried: it is where the engulfment genes' pro-death role was measured (Reddien 2001; Hoeppner 2001), not a mechanism, and the role is non-core for this gene.
Supporting Evidence:
PMID:23505386
the extra cell corpses in ced-1 mutant larvae likely reflected an engulfment defect
PMID:23505386
Given that ced-1 and other genes that function in cell-corpse engulfment promote programmed cell death
PMID:11449278
mutations in engulfment genes alone allow the survival and differentiation of some cells that would normally die
PMID:11449278
the expression in engulfing cells of ced-1, which encodes a receptor that recognizes cell corpses, rescues the cell-killing defects of ced-1 mutants
PMID:11449279
genes that mediate corpse removal can also function to actively kill cells
GO:1904747 positive regulation of apoptotic process involved in development
IGI
PMID:23505386
Both the caspase CSP-1 and a caspase-independent pathway pro...
MODIFY
Summary: Positive regulation of apoptotic process involved in development (Denning et al. 2013).
Reason: The cited paper uses ced-1 as a background and attributes the extra corpses to an engulfment defect, so it does not itself show this. The term is still supported elsewhere: engulfment genes, including ced-1 acting in engulfing cells, promote death of cells receiving weak death signals (Reddien 2001; Hoeppner 2001), which the Denning paper also states. The role is non-core, a consequence of the engulfment role. The claim is positive regulation of apoptotic process (GO:0043065); the precomposed term's developmental context is dropped.
Context of precomposed term: context dropped
Decomposed from the precomposed GO:1904747 positive regulation of apoptotic process involved in development (projects/INVOLVED_IN_PRECOMPOSITION.md, round 6), which positively regulates GO:1902742 apoptotic process involved in development, to the regulation genus GO:0043065. The developmental context is not carried: it is where the engulfment genes' pro-death role was measured (Reddien 2001; Hoeppner 2001), not a mechanism, and the role is non-core for this gene.
Supporting Evidence:
PMID:23505386
the extra cell corpses in ced-1 mutant larvae likely reflected an engulfment defect
PMID:23505386
Given that ced-1 and other genes that function in cell-corpse engulfment promote programmed cell death
PMID:11449278
mutations in engulfment genes alone allow the survival and differentiation of some cells that would normally die
PMID:11449278
the expression in engulfing cells of ced-1, which encodes a receptor that recognizes cell corpses, rescues the cell-killing defects of ced-1 mutants
PMID:11449279
genes that mediate corpse removal can also function to actively kill cells
GO:1904747 positive regulation of apoptotic process involved in development
IGI
PMID:23505386
Both the caspase CSP-1 and a caspase-independent pathway pro...
MODIFY
Summary: Positive regulation of apoptotic process involved in development (Denning et al. 2013).
Reason: The cited paper uses ced-1 as a background and attributes the extra corpses to an engulfment defect, so it does not itself show this. The term is still supported elsewhere: engulfment genes, including ced-1 acting in engulfing cells, promote death of cells receiving weak death signals (Reddien 2001; Hoeppner 2001), which the Denning paper also states. The role is non-core, a consequence of the engulfment role. The claim is positive regulation of apoptotic process (GO:0043065); the precomposed term's developmental context is dropped.
Context of precomposed term: context dropped
Decomposed from the precomposed GO:1904747 positive regulation of apoptotic process involved in development (projects/INVOLVED_IN_PRECOMPOSITION.md, round 6), which positively regulates GO:1902742 apoptotic process involved in development, to the regulation genus GO:0043065. The developmental context is not carried: it is where the engulfment genes' pro-death role was measured (Reddien 2001; Hoeppner 2001), not a mechanism, and the role is non-core for this gene.
Supporting Evidence:
PMID:23505386
the extra cell corpses in ced-1 mutant larvae likely reflected an engulfment defect
PMID:23505386
Given that ced-1 and other genes that function in cell-corpse engulfment promote programmed cell death
PMID:11449278
mutations in engulfment genes alone allow the survival and differentiation of some cells that would normally die
PMID:11449278
the expression in engulfing cells of ced-1, which encodes a receptor that recognizes cell corpses, rescues the cell-killing defects of ced-1 mutants
PMID:11449279
genes that mediate corpse removal can also function to actively kill cells
GO:1904747 positive regulation of apoptotic process involved in development
IMP
PMID:23505386
Both the caspase CSP-1 and a caspase-independent pathway pro...
MODIFY
Summary: Positive regulation of apoptotic process involved in development (Denning et al. 2013).
Reason: The cited paper uses ced-1 as a background and attributes the extra corpses to an engulfment defect, so it does not itself show this. The term is still supported elsewhere: engulfment genes, including ced-1 acting in engulfing cells, promote death of cells receiving weak death signals (Reddien 2001; Hoeppner 2001), which the Denning paper also states. The role is non-core, a consequence of the engulfment role. The claim is positive regulation of apoptotic process (GO:0043065); the precomposed term's developmental context is dropped.
Context of precomposed term: context dropped
Decomposed from the precomposed GO:1904747 positive regulation of apoptotic process involved in development (projects/INVOLVED_IN_PRECOMPOSITION.md, round 6), which positively regulates GO:1902742 apoptotic process involved in development, to the regulation genus GO:0043065. The developmental context is not carried: it is where the engulfment genes' pro-death role was measured (Reddien 2001; Hoeppner 2001), not a mechanism, and the role is non-core for this gene.
Supporting Evidence:
PMID:23505386
the extra cell corpses in ced-1 mutant larvae likely reflected an engulfment defect
PMID:23505386
Given that ced-1 and other genes that function in cell-corpse engulfment promote programmed cell death
PMID:11449278
mutations in engulfment genes alone allow the survival and differentiation of some cells that would normally die
PMID:11449278
the expression in engulfing cells of ced-1, which encodes a receptor that recognizes cell corpses, rescues the cell-killing defects of ced-1 mutants
PMID:11449279
genes that mediate corpse removal can also function to actively kill cells

Core Functions

Engulfment receptor on engulfing cells that recognizes apoptotic cell corpses through the PtdSer-bridging ligand TTR-52 and drives their engulfment.

Supporting Evidence:
  • PMID:11163239
    CED-1 is a cell surface phagocytic receptor that recognizes cell corpses
  • PMID:20526330
    binds to both PtdSer and the extracellular domain of CED-1 in vitro
  • PMID:22713871
    CED-1 binds TTR-52 through its N-terminal EMI domain
  • PMID:11163239
    ced-1 is expressed in and functions in engulfing cells

Signals through its cytoplasmic NPXY motif to the CED-6 adaptor and DYN-1 to drive actin reorganization, internalization and phagosome maturation into a phagolysosome.

Supporting Evidence:
  • PMID:11729193
    we present evidence for a physical interaction between GULP/CED-6 and one of the two motifs (NPXY motif) in the cytoplasmic tail of CED-1
  • PMID:11163239
    Motifs in the intracellular domain of CED-1 known to interact with PTB and SH2 domains were necessary for engulfment but not for clustering
  • PMID:18351800
    One of the pathways, composed of CED-1, the adaptor protein CED-6, and DYN-1, controls the rate of enrichment of PI(3)P and RAB-7 on phagosomal surfaces and the formation of phagolysosomes
  • PMID:15744306
    CED-1, CED-6 and CED-7 are required for actin reorganization around the apoptotic cell corpse

References

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Suggested Questions for Experts

Q: Does CED-1 bind phosphatidylserine directly, or only through TTR-52 and other bridging molecules?

Q: How do engulfing cells, through CED-1, push cells that have received a weak death signal into death, and what signal passes back to the dying cell?

Q: Should the PANTHER family for CED-1 follow PANTHER's own classification (PTHR24035:SF109, which holds the CED-1/Draper/MEGF10 PAINT nodes) rather than the UniProt/InterPro cross-reference (PTHR24043:SF8)? See projects/PANTHER_FAMILY_ASSIGNMENT_DISCREPANCIES.md.

Suggested Experiments

Experiment: In a weak ced-3 background, compare survival of specific cells when ced-1 is restored only in the engulfing cell versus with NPXY or YXXL tail mutants, scoring survival with cell-type reporters.

Hypothesis: CED-1 promotes death of weakly signalled cells through direct contact-dependent signalling from the engulfing cell.

Type: genetic

Deep Research

WormBase

(ced-1-deep-research-wormbase.md)

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πŸ“š Additional Documentation

Notes

(ced-1-notes.md)

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πŸ“„ View Raw YAML

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