MEGF10 is a single-pass type I transmembrane receptor of the CED-1/Draper family, made of an EMI domain, 17 atypical EGF-like repeats and a cytoplasmic tail with NPxY and YxxL motifs. It is the mammalian functional ortholog of the C. elegans engulfment receptor CED-1 and is classified as a class F scavenger receptor. On astrocytes and other engulfing cells it binds the eat-me signal C1q, which marks phosphatidylserine-exposing apoptotic cells. It collects at the base of the forming phagocytic cup and drives engulfment, working with the CED-6 ortholog GULP1 and the CED-7 ortholog ABCA1. Astrocytes also use it to engulf synapses during synapse elimination. In the retina, homotypic MEGF10 signalling causes cell-cell repulsion that spaces starburst amacrine and horizontal cells into mosaics. In skeletal muscle it is expressed in satellite cells and regulates myoblast proliferation, migration and differentiation, in part through Notch1. Recessive loss of function causes early-onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001849 complement component C1q complex binding | IDA PMID:27170117 Megf10 Is a Receptor for C1Q That Mediates Clearance of Apop... | ACCEPT | Summary: Direct high-affinity binding of MEGF10 to C1q, an eat-me signal that binds phosphatidylserine on apoptotic cells. Reason: IDA from Iram et al. 2016. C1q is the best-characterized ligand through which MEGF10 recognizes apoptotic cells, and EMARDD mutations impair both C1q binding and clearance. This is the ligand-recognition part of the core receptor function. Supporting Evidence: PMID:27170117 Megf10 binds with high affinity to C1q, an eat-me signal for apoptotic cells PMID:27170117 cells expressing Megf10 with EMARDD mutations have impaired apoptotic cell clearance and impaired binding to C1q |
| GO:0001891 phagocytic cup | IBA GO_REF:0000033 | ACCEPT | Summary: MEGF10 is active at the phagocytic cup (IBA from PTN002778616). Reason: Consistent with direct imaging of MEGF10 recruitment to the forming phagocytic cup during apoptotic-cell engulfment. Supporting Evidence: PMID:17205124 is recruited at the bottom of the forming phagocytic cup |
| GO:0001891 phagocytic cup | IDA PMID:17205124 Cooperation between engulfment receptors: the case of ABCA1 ... | ACCEPT | Summary: MEGF10 is recruited to the base of the forming phagocytic cup during engulfment of apoptotic thymocytes. Reason: The full text of Hamon et al. 2006 shows MEGF10 imaged at the phagocytic cup. This is the location where the engulfment receptor acts. Supporting Evidence: PMID:17205124 is recruited at the bottom of the forming phagocytic cup |
| GO:0001891 phagocytic cup | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic phagocytic cup annotation, consistent with experimental data. Reason: Agrees with the IDA and IBA annotations to the same term. Supporting Evidence: PMID:17205124 is recruited at the bottom of the forming phagocytic cup |
| GO:0005044 scavenger receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Scavenger receptor activity (IBA, PTN009076277, sources include C. elegans ced-1). Reason: MEGF10 is the class F scavenger receptor SR-F3. GO:0005044 explicitly lists apoptotic cells and amyloid-beta fibrils as ligands, both of which MEGF10 takes up. The IBA node groups MEGF10 with CED-1, which supports a conserved receptor function. MEGF10 appearing among the sources is expected because it has its own IDA. Note: the UniProt PANTHER cross-reference (PTHR24052) differs from the PANTHER family that carries this node (see projects/PANTHER_FAMILY_ASSIGNMENT_DISCREPANCIES.md). Supporting Evidence: PMID:27170117 Multiple EGF-like domains 10 (Megf10) is a class F scavenger receptor (SR-F3) PMID:27170117 cells transfected with Megf10 gain the ability to phagocytose apoptotic neurons |
| GO:0005044 scavenger receptor activity | IDA PMID:27170117 Megf10 Is a Receptor for C1Q That Mediates Clearance of Apop... | ACCEPT | Summary: MEGF10 confers phagocytosis of apoptotic neurons when expressed and is a class F scavenger receptor. Reason: IDA from Iram et al. 2016. Core molecular function. Supporting Evidence: PMID:27170117 Multiple EGF-like domains 10 (Megf10) is a class F scavenger receptor (SR-F3) PMID:27170117 cells transfected with Megf10 gain the ability to phagocytose apoptotic neurons |
| GO:0005112 Notch binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Notch binding by IBA (PTN002778616, vertebrate MEGF10 clade). Reason: The underlying evidence is co-immunoprecipitation of the MEGF10 and Notch1 intracellular domains in myoblasts. It may contribute to muscle phenotypes but is not the conserved engulfment function. MEGF10 loss causes EMARDD myopathy, and satellite-cell/myoblast phenotypes are well documented. These muscle roles are real but separate from the conserved engulfment-receptor function, and their mechanism (including the Notch1 interaction) is incompletely defined, so they are kept as non-core. Supporting Evidence: PMID:28498977 Reciprocal co-immunoprecipitation studies show that Megf10 and Notch1 interact via their respective intracellular domains |
| GO:0005112 Notch binding | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Electronic Notch binding annotation. Reason: Same basis as the IPI/IBA rows. MEGF10 loss causes EMARDD myopathy, and satellite-cell/myoblast phenotypes are well documented. These muscle roles are real but separate from the conserved engulfment-receptor function, and their mechanism (including the Notch1 interaction) is incompletely defined, so they are kept as non-core. Supporting Evidence: PMID:28498977 Reciprocal co-immunoprecipitation studies show that Megf10 and Notch1 interact via their respective intracellular domains |
| GO:0005112 Notch binding | IPI PMID:28498977 Consequences of MEGF10 deficiency on myoblast function and N... | KEEP AS NON CORE | Summary: Megf10 and Notch1 co-immunoprecipitate via their intracellular domains. Reason: IPI from Saha et al. 2017. The interaction is weakened by the EMARDD C774R mutation, which suggests relevance to myopathy. It is reported as a cytoplasmic-domain interaction, not ligand-receptor binding. MEGF10 loss causes EMARDD myopathy, and satellite-cell/myoblast phenotypes are well documented. These muscle roles are real but separate from the conserved engulfment-receptor function, and their mechanism (including the Notch1 interaction) is incompletely defined, so they are kept as non-core. Supporting Evidence: PMID:28498977 Reciprocal co-immunoprecipitation studies show that Megf10 and Notch1 interact via their respective intracellular domains |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane (IBA). Reason: MEGF10 is a single-pass type I cell-surface receptor. Supporting Evidence: PMID:17205124 MEGF10 was translated as 170 kDa protein targeted to the plasma membrane |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Plasma membrane by immunofluorescence (HPA). Reason: Consistent with surface biotinylation and imaging data. Supporting Evidence: PMID:17205124 MEGF10 was translated as 170 kDa protein targeted to the plasma membrane |
| GO:0005886 plasma membrane | IDA PMID:27170117 Megf10 Is a Receptor for C1Q That Mediates Clearance of Apop... | ACCEPT | Summary: Plasma membrane localization (IDA). Reason: Cell-surface receptor. Consistent with all localization data. Supporting Evidence: PMID:17205124 MEGF10 was translated as 170 kDa protein targeted to the plasma membrane PMID:17498693 MEGF10 protein accumulated around the contact region during engulfment of apoptotic cells |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic plasma membrane annotation. Reason: Correct location for a type I transmembrane receptor. Supporting Evidence: PMID:17205124 MEGF10 was translated as 170 kDa protein targeted to the plasma membrane |
| GO:0014719 skeletal muscle satellite cell activation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Satellite cell activation, transferred from mouse Megf10. Reason: Electronic annotation. No cited study assays the quiescence-to-activation transition itself. Holterman et al. 2007 describe Megf10 as a marker of quiescent satellite cells and show that silencing it in already-activated satellite cells reduces their number through myogenin activation and precocious differentiation, which is a differentiation phenotype rather than a failure to activate. Logan et al. 2011 report expression in activated satellite cells, which is not participation in activation. The proliferation and differentiation terms already capture what was shown. Supporting Evidence: PMID:18056409 Megf10 silencing in activated satellite cells on individual fibers or in cultured myoblasts results in a dramatic reduction in the cell number, caused by myogenin activation and precocious differentiation PMID:18056409 as a quiescent satellite cell marker that is also expressed in skeletal myoblasts but not in differentiated myofibers |
| GO:0014719 skeletal muscle satellite cell activation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Satellite cell activation (ISS from mouse Megf10). Reason: Transferred from mouse Megf10. No cited study assays the quiescence-to-activation transition itself. Holterman et al. 2007 describe Megf10 as a marker of quiescent satellite cells and show that silencing it in already-activated satellite cells reduces their number through myogenin activation and precocious differentiation, which is a differentiation phenotype rather than a failure to activate. Logan et al. 2011 report expression in activated satellite cells, which is not participation in activation. The proliferation and differentiation terms already capture what was shown. Supporting Evidence: PMID:18056409 Megf10 silencing in activated satellite cells on individual fibers or in cultured myoblasts results in a dramatic reduction in the cell number, caused by myogenin activation and precocious differentiation PMID:18056409 as a quiescent satellite cell marker that is also expressed in skeletal myoblasts but not in differentiated myofibers |
| GO:0014816 skeletal muscle satellite cell differentiation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Satellite cell differentiation (electronic). Reason: Electronic annotation. Silencing Megf10 causes precocious differentiation of satellite cells and overexpression inhibits differentiation, so Megf10 restrains satellite-cell differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:18056409 Megf10 silencing in activated satellite cells on individual fibers or in cultured myoblasts results in a dramatic reduction in the cell number, caused by myogenin activation and precocious differentiation PMID:18056409 Retroviral expression of Megf10 in myoblasts results in enhanced proliferation and inhibited differentiation |
| GO:0014816 skeletal muscle satellite cell differentiation | IMP PMID:22101682 Mutations in MEGF10, a regulator of satellite cell myogenesi... | KEEP AS NON CORE | Summary: MEGF10 regulates satellite cell differentiation and fusion; mutations cause EMARDD. Reason: IMP from PMID:22101682. Silencing Megf10 causes precocious differentiation of satellite cells and overexpression inhibits differentiation, so Megf10 restrains satellite-cell differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:22101682 MEGF10 is highly expressed in activated satellite cells and regulates their proliferation as well as their differentiation and fusion into multinucleated myofibers PMID:18056409 Megf10 silencing in activated satellite cells on individual fibers or in cultured myoblasts results in a dramatic reduction in the cell number, caused by myogenin activation and precocious differentiation PMID:18056409 Retroviral expression of Megf10 in myoblasts results in enhanced proliferation and inhibited differentiation |
| GO:0014841 skeletal muscle satellite cell proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Satellite cell proliferation (electronic). Reason: Electronic annotation. Megf10 overexpression enhances myoblast proliferation and silencing depletes the satellite-cell pool, supporting a role in sustaining satellite-cell proliferation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:18056409 Retroviral expression of Megf10 in myoblasts results in enhanced proliferation and inhibited differentiation PMID:18056409 Megf10 represents a novel transmembrane protein that impinges on Notch signaling to regulate the satellite cell population balance between proliferation and differentiation |
| GO:0014841 skeletal muscle satellite cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Satellite cell proliferation (ISS from mouse). Reason: Transferred from mouse Megf10. Megf10 overexpression enhances myoblast proliferation and silencing depletes the satellite-cell pool, supporting a role in sustaining satellite-cell proliferation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:18056409 Retroviral expression of Megf10 in myoblasts results in enhanced proliferation and inhibited differentiation PMID:18056409 Megf10 represents a novel transmembrane protein that impinges on Notch signaling to regulate the satellite cell population balance between proliferation and differentiation |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000108 | MARK AS OVER ANNOTATED | Summary: Vesicle-mediated transport, inferred from scavenger receptor activity. Reason: Vesicle-mediated transport is a correct but uninformative parent of receptor-mediated engulfment. The informative process, engulfment of apoptotic cell (GO:0043652), is already annotated, so this broad inference adds no information. Supporting Evidence: PMID:27170117 cells transfected with Megf10 gain the ability to phagocytose apoptotic neurons |
| GO:0022409 positive regulation of cell-cell adhesion | IMP PMID:31267131 Selective serotonin reuptake inhibitors ameliorate MEGF10 my... | UNDECIDED | Summary: Positive regulation of cell-cell adhesion (IMP, Saha et al. 2019). Reason: The cached record for PMID:31267131 is abstract-only and the abstract describes a drug screen on myoblast proliferation. It does not mention cell-cell adhesion, so the evidence behind this IMP cannot be checked here. MEGF10 adhesion phenotypes have been reported (strong substrate adhesion of MEGF10-expressing cells), so the annotation is not obviously wrong. Left undecided pending full-text review. Supporting Evidence: PMID:31267131 A primary in vitro drug screen assessed cellular proliferation patterns in Megf10-deficient myoblasts |
| GO:0033002 muscle cell proliferation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Muscle cell proliferation (ARBA). Reason: Electronic annotation. Megf10 knockdown, the EMARDD C774R mutation and Megf10 knockout all impair myoblast proliferation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:28498977 leads to impaired proliferation and migration of C2C12 cells PMID:28498977 Myoblasts from Megf10-/- mice and Megf10-/-/mdx double knockout (dko) mice also show impaired proliferation and migration |
| GO:0033002 muscle cell proliferation | IMP PMID:28498977 Consequences of MEGF10 deficiency on myoblast function and N... | KEEP AS NON CORE | Summary: Megf10 knockdown or deficiency impairs myoblast proliferation. Reason: IMP from PMID:28498977. Megf10 knockdown, the EMARDD C774R mutation and Megf10 knockout all impair myoblast proliferation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:28498977 leads to impaired proliferation and migration of C2C12 cells PMID:28498977 Myoblasts from Megf10-/- mice and Megf10-/-/mdx double knockout (dko) mice also show impaired proliferation and migration |
| GO:0034109 homotypic cell-cell adhesion | IDA PMID:22407321 MEGF10 and MEGF11 mediate homotypic interactions required fo... | MODIFY | Summary: Homotypic cell-cell adhesion (IDA, Kay et al. 2012, retinal mosaics). Reason: The full text of PMID:22407321 shows that MEGF10 mediates homotypic recognition that produces intercellular repulsion, not adhesion. MEGF10-expressing HEK293 cells formed sharp borders with gaps, and no homophilic binding was detected. GO:0034109 (attachment of a cell to a second cell of the identical type via adhesion molecules) therefore contradicts the reported phenotype. The supported part is homotypic cell-cell recognition. GO has no 'homotypic cell-cell repulsion' term, so the nearest accurate parent is proposed. Proposed replacements: cell-cell recognition Supporting Evidence: PMID:22407321 these results suggest that a MEGF10-containing signaling complex mediates a homotypic interaction resulting in intercellular repulsion PMID:22407321 we have been unable to demonstrate MEGF10 homophilic binding using biochemical methods PMID:22407321 mosaic spacing requires repellent homotypic interactions mediated by MEGF10 and 11 |
| GO:0043652 engulfment of apoptotic cell | IBA GO_REF:0000033 | ACCEPT | Summary: Engulfment of apoptotic cell (IBA, PTN002372116; sources ced-1, Draper and mouse Megf10). Reason: The node is the CED-1/Draper/MEGF10 engulfment-receptor clade. MEGF10 is the mammalian CED-1 ortholog. It is a transmembrane engulfment receptor that recognizes apoptotic cells (through C1q bound to phosphatidylserine) and drives their phagocytosis. This is its conserved core function. Supporting Evidence: PMID:17205124 MEGF10, a novel receptor bearing striking structural similarities to CED-1, as a bona fide functional ortholog in mammals PMID:27170117 cells transfected with Megf10 gain the ability to phagocytose apoptotic neurons PMID:27170117 Megf10-deficient mice have increased apoptotic cells in the developing cerebellum and have impaired phagocytosis of apoptotic cells by astrocytes |
| GO:0043652 engulfment of apoptotic cell | ISS GO_REF:0000024 | ACCEPT | Summary: Engulfment of apoptotic cell (ISS from mouse Megf10 IMP). Reason: MEGF10 is the mammalian CED-1 ortholog. It is a transmembrane engulfment receptor that recognizes apoptotic cells (through C1q bound to phosphatidylserine) and drives their phagocytosis. This is its conserved core function. Supporting Evidence: PMID:27170117 Megf10-deficient mice have increased apoptotic cells in the developing cerebellum and have impaired phagocytosis of apoptotic cells by astrocytes PMID:27170117 cells transfected with Megf10 gain the ability to phagocytose apoptotic neurons |
| GO:0048468 cell development | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Cell development (ARBA). Reason: Too general to be informative. The more specific muscle-development rows cover this aspect, and none of it is core. Supporting Evidence: PMID:22101682 MEGF10 is highly expressed in activated satellite cells and regulates their proliferation as well as their differentiation and fusion into multinucleated myofibers |
| GO:0048627 myoblast development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Myoblast development (electronic, from mouse). Reason: Electronic annotation. Megf10 is expressed in myoblasts but not differentiated myofibers and keeps myoblasts proliferating while inhibiting their differentiation, so it shapes myoblast progression. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:18056409 as a quiescent satellite cell marker that is also expressed in skeletal myoblasts but not in differentiated myofibers PMID:18056409 Retroviral expression of Megf10 in myoblasts results in enhanced proliferation and inhibited differentiation |
| GO:0048641 regulation of skeletal muscle tissue development | IMP PMID:22101682 Mutations in MEGF10, a regulator of satellite cell myogenesi... | KEEP AS NON CORE | Summary: Regulation of skeletal muscle tissue development (IMP, EMARDD). Reason: IMP from PMID:22101682. Loss of MEGF10 in EMARDD reduces satellite-cell-derived myofibers, and Megf10 balances satellite-cell proliferation against differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:22101682 fusion into multinucleated myofibers, which are greatly reduced in muscle from individuals with early onset myopathy, areflexia, respiratory distress and dysphagia PMID:18056409 Megf10 represents a novel transmembrane protein that impinges on Notch signaling to regulate the satellite cell population balance between proliferation and differentiation |
| GO:0051147 regulation of muscle cell differentiation | IMP PMID:22101682 Mutations in MEGF10, a regulator of satellite cell myogenesi... | KEEP AS NON CORE | Summary: Regulation of muscle cell differentiation (IMP). Reason: IMP from PMID:22101682. Megf10 overexpression inhibits myoblast differentiation and silencing causes precocious differentiation, a direct regulatory phenotype for muscle cell differentiation. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:22101682 MEGF10 is highly expressed in activated satellite cells and regulates their proliferation as well as their differentiation and fusion into multinucleated myofibers PMID:18056409 Retroviral expression of Megf10 in myoblasts results in enhanced proliferation and inhibited differentiation PMID:18056409 Megf10 silencing in activated satellite cells on individual fibers or in cultured myoblasts results in a dramatic reduction in the cell number, caused by myogenin activation and precocious differentiation |
| GO:0051451 myoblast migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Myoblast migration (IBA, PTN002778616). Reason: IBA. Megf10 knockdown and Megf10-/- myoblasts show impaired migration. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:28498977 leads to impaired proliferation and migration of C2C12 cells PMID:28498977 Myoblasts from Megf10-/- mice and Megf10-/-/mdx double knockout (dko) mice also show impaired proliferation and migration |
| GO:0051451 myoblast migration | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Myoblast migration (electronic). Reason: Electronic annotation. Megf10 knockdown and Megf10-/- myoblasts show impaired migration. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:28498977 leads to impaired proliferation and migration of C2C12 cells PMID:28498977 Myoblasts from Megf10-/- mice and Megf10-/-/mdx double knockout (dko) mice also show impaired proliferation and migration |
| GO:0051451 myoblast migration | IMP PMID:28498977 Consequences of MEGF10 deficiency on myoblast function and N... | KEEP AS NON CORE | Summary: Megf10 deficiency impairs myoblast migration. Reason: IMP from PMID:28498977. Megf10 knockdown and Megf10-/- myoblasts show impaired migration. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:28498977 leads to impaired proliferation and migration of C2C12 cells PMID:28498977 Myoblasts from Megf10-/- mice and Megf10-/-/mdx double knockout (dko) mice also show impaired proliferation and migration |
| GO:0055001 muscle cell development | IMP PMID:22101682 Mutations in MEGF10, a regulator of satellite cell myogenesi... | KEEP AS NON CORE | Summary: Muscle cell development (IMP, EMARDD). Reason: IMP from PMID:22101682. MEGF10 regulates satellite-cell differentiation and fusion into multinucleated myofibers, which are reduced in EMARDD muscle. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:22101682 fusion into multinucleated myofibers, which are greatly reduced in muscle from individuals with early onset myopathy, areflexia, respiratory distress and dysphagia |
| GO:1902742 apoptotic process involved in development | ISS GO_REF:0000024 | REMOVE | Summary: Apoptotic process involved in development (ISS from mouse Megf10 IMP, PMID:27170117). Reason: This ISS is transferred from the mouse Megf10 IMP (MGI, PMID:27170117). The source phenotype is more TUNEL- and cleaved-caspase-3-positive cells in the developing cerebellum of Megf10-deficient mice, which the authors read as a clearance defect. In the full text (PMC4863057, checked for this review) the Figure 1 title says that Megf10 deficiency 'results in accumulation of apoptotic cells in the developing CB'. Uncleared corpses accumulate whether or not more cells die. MEGF10 acts in the engulfing cell (engulfment of apoptotic cell, which GO separates from the apoptotic process itself) and does none of the work of the apoptotic program. The mouse source row is also REMOVE in genes/mouse/Megf10/Megf10-ai-review.yaml. This case is logged in projects/APOPTOSIS/ASSAY_READOUT_OVERANNOTATION.md. Propagation Review Root cause: SOURCE BAD Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q6DIB5 · Megf10 SOURCE BAD Mouse IMP (MGI, PMID:27170117) annotates an accumulation of uncleared apoptotic cells as participation in the apoptotic process. Reviewed as REMOVE in the mouse Megf10 review. Supporting Evidence: PMID:27170117 Megf10-deficient mice have increased apoptotic cells in the developing cerebellum and have impaired phagocytosis of apoptotic cells by astrocytes |
| GO:2000288 positive regulation of myoblast proliferation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Positive regulation of myoblast proliferation (electronic). Reason: Electronic annotation. Megf10 overexpression enhances myoblast proliferation and Megf10-deficient myoblasts proliferate poorly. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. Supporting Evidence: PMID:18056409 Retroviral expression of Megf10 in myoblasts results in enhanced proliferation and inhibited differentiation PMID:28498977 Myoblasts from Megf10-/- mice and Megf10-/-/mdx double knockout (dko) mice also show impaired proliferation and migration PMID:23954233 Overexpression of wild-type MEGF10 enhanced C2C12 myoblast proliferation, while overexpression of Y1030F mutated MEGF10 did not |
| GO:2000288 positive regulation of myoblast proliferation | IMP PMID:31267131 Selective serotonin reuptake inhibitors ameliorate MEGF10 my... | KEEP AS NON CORE | Summary: Positive regulation of myoblast proliferation (IMP, Saha et al. 2019). Reason: IMP from PMID:31267131. Megf10 overexpression enhances myoblast proliferation and Megf10-deficient myoblasts proliferate poorly. This muscle role is real but separate from the conserved engulfment-receptor function, so it is kept as non-core. The cached record of PMID:31267131 is abstract-only and its abstract reports no result for this term, so the source paper is not quoted here; the term is supported by the other cited studies. Supporting Evidence: PMID:18056409 Retroviral expression of Megf10 in myoblasts results in enhanced proliferation and inhibited differentiation PMID:28498977 Myoblasts from Megf10-/- mice and Megf10-/-/mdx double knockout (dko) mice also show impaired proliferation and migration PMID:23954233 Overexpression of wild-type MEGF10 enhanced C2C12 myoblast proliferation, while overexpression of Y1030F mutated MEGF10 did not |
| GO:0098883 synapse pruning | IMP PMID:24270812 Astrocytes mediate synapse elimination through MEGF10 and ME... | NEW | Summary: Astrocyte engulfment of synapses requires MEGF10 (mouse). Reason: In the developing and adult mouse brain, astrocytes engulf synapses through MEGF10 and MERTK. MEGF10 is the engulfment receptor in this process, so it does part of the work of synapse removal. This is not just a requirement. Comparator check: other phagocytic receptors used for synapse removal carry this branch (ITGAM, the CR3 alpha chain, carries complement-mediated synapse pruning GO:0150062; C1QA carries GO:0098883). Synapse removal uses the same scavenger-receptor engulfment activity as apoptotic-cell clearance, acting on a different target, so it is listed under the core engulfment function. Supporting Evidence: PMID:24270812 requires the MEGF10 and MERTK phagocytic pathways PMID:24270812 Both MEGF10 and MERTK function as engulfment receptors |
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Download this section (compressed HTML)Q: Does MEGF10 bind phosphatidylserine directly, or does it recognize apoptotic cells only through bridging molecules such as C1q?
Q: What is the ligand for the homotypic MEGF10-dependent repulsion that spaces retinal neurons, given that MEGF10 homophilic binding was not detected biochemically?
Q: Is the MEGF10-Notch1 intracellular-domain interaction direct, and does it explain the satellite-cell proliferation and differentiation phenotypes in EMARDD?
Q: Should PANTHER family grounding for MEGF10 follow PANTHER's own classification (PTHR24035:SF136, the family that carries the CED-1/Draper PAINT nodes) rather than the UniProt/InterPro cross-reference (PTHR24052:SF13)? See projects/PANTHER_FAMILY_ASSIGNMENT_DISCREPANCIES.md.
Q: Is MEGF10 expressed mainly in quiescent satellite cells (Holterman et al. 2007, mouse) or in activated satellite cells (Logan et al. 2011, human), and does its role differ between the two states?
Experiment: Liposome flotation and SPR binding of purified MEGF10 ectodomain to PS-containing versus PC-only liposomes, with and without C1q, including EMARDD missense variants.
Hypothesis: The MEGF10 ectodomain binds phosphatidylserine directly, independently of C1q.
Type: binding assay
Experiment: Compare engulfment of apoptotic cells by MEGF10 wild-type, NPxY-mutant and Y1030F-mutant receptors in GULP1-knockout versus control phagocytes.
Hypothesis: GULP1 couples MEGF10 to engulfment through the NPxY motif.
Type: genetic and cell biological
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