GLP-1 is one of the two Caenorhabditis elegans Notch-family receptors. It is a single-pass type I membrane protein with 10 EGF-like repeats, three LIN-12/Notch repeats, and an intracellular RAM domain and ankyrin repeats. In the germ line GLP-1 receives the DSL ligands LAG-2 and APX-1 from the distal tip cell niche. Its intracellular domain binds the CSL transcription factor LAG-1 and recruits the Mastermind-like coactivator LAG-3/SEL-8 to activate transcription of sygl-1 and lst-1. This keeps germ cells in the proliferative stem-cell state and prevents entry into meiosis. Maternal glp-1 mRNA is translationally controlled so that GLP-1 accumulates in anterior (AB) blastomeres. There it receives APX-1 from P2 to specify ABp and ABa descendant fates, including the anterior pharynx. GLP-1 acts redundantly with LIN-12 in many embryonic cell interactions. It also works in dauer neurons to maintain the dauer state and modulates oocyte growth. Temperature-sensitive glp-1 mutants raised at the restrictive temperature lack a germ line and live longer than wild type; this lifespan extension is a consequence of germline loss, which acts through PHA-4-induced autophagy and the lipase LIPL-4 in somatic tissues.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001555 oocyte growth | IGI PMID:19502484 MSP and GLP-1/Notch signaling coordinately regulate actomyos... | KEEP AS NON CORE | Summary: GLP-1 signaling modulates MSP-dependent oocyte growth. Reason: Supported biological role that is a downstream output of GLP-1/Notch signaling rather than a core molecular activity. Supporting Evidence: PMID:19502484 we show that GLP-1/Notch signaling functions in the germline to modulate oocyte growth when sperm are available for fertilization and the major sperm protein (MSP) hormone is present. |
| GO:0001555 oocyte growth | IMP PMID:19502484 MSP and GLP-1/Notch signaling coordinately regulate actomyos... | KEEP AS NON CORE | Summary: glp-1 reduction-of-function produces enlarged oocytes. Reason: Supported biological role that is a downstream output of GLP-1/Notch signaling rather than a core molecular activity. Supporting Evidence: PMID:19502484 we show that GLP-1/Notch signaling functions in the germline to modulate oocyte growth when sperm are available for fertilization and the major sperm protein (MSP) hormone is present. |
| GO:0001708 cell fate specification | IEA GO_REF:0000117 | ACCEPT | Summary: Cell fate specification (ARBA IEA). Reason: GLP-1 specifies embryonic blastomere fates and the germline stem-cell fate. Supporting Evidence: PMID:32196486 In the C. elegans germline, GLP-1 Notch signaling specifies the stem cell fate, employing the sequence-specific DNA binding protein LAG-1 to implement the transcriptional response. |
| GO:0001708 cell fate specification | IGI PMID:1769331 Two homologous regulatory genes, lin-12 and glp-1, have over... | ACCEPT | Summary: lin-12 glp-1 double mutants have widespread cell-fate defects (Lag phenotype). Reason: Redundant cell-fate specification with LIN-12 in the embryo. Supporting Evidence: PMID:1769331 We show here that lin-12 and glp-1 are functionally redundant during embryogenesis: Unlike either single mutant, the lin-12 glp-1 double mutant dies soon after hatching. |
| GO:0002119 nematode larval development | IGI PMID:1769331 Two homologous regulatory genes, lin-12 and glp-1, have over... | KEEP AS NON CORE | Summary: lin-12 glp-1 double mutants die as L1 larvae. Reason: Larval lethality is a pleiotropic consequence of failed embryonic cell-fate decisions. Supporting Evidence: PMID:1769331 We show here that lin-12 and glp-1 are functionally redundant during embryogenesis: Unlike either single mutant, the lin-12 glp-1 double mutant dies soon after hatching. |
| GO:0003713 transcription coactivator activity | IDA PMID:9003776 Roles of the RAM and ANK domains in signaling by the C. eleg... | ACCEPT | Summary: The GLP-1 intracellular ANK repeats activate transcription and bind LAG-1. Reason: The NICD acts as a coactivator for the DNA-binding CSL factor LAG-1 and recruits LAG-3. Transcription coactivator activity is the appropriate MF for the nuclear intracellular domain (as for NOTCH1 NICD). Supporting Evidence: PMID:9003776 Finally, we show in yeast that the ANK repeats are strong transcriptional activators. PMID:9003776 We speculate that one possible function for the ANK repeat domain is to act as a transcriptional co-activator with LAG-1. PMID:10830967 We propose that GLP-1 and LIN-12 promote signalling by recruiting LAG-3 to target promoters, where it functions as a transcriptional activator. |
| GO:0004888 transmembrane signaling receptor activity | IC PMID:7607080 GLP-1 is localized to the mitotic region of the C. elegans g... | ACCEPT | Summary: GLP-1 is an integral membrane receptor for the distal tip cell signal. Reason: Core molecular function. Supporting Evidence: PMID:7607080 GLP-1 is tightly associated with membranes of mitotic germline cells, supporting its identification as an integral membrane protein. PMID:7607080 consistent with the model that GLP-1 acts as a membrane receptor for the distal tip cell signal |
| GO:0004888 transmembrane signaling receptor activity | ISS PMID:1457827 Molecular basis of loss-of-function mutations in the glp-1 g... | ACCEPT | Summary: Similarity to Notch receptors and mutations in EGF/LNR/ANK repeats. Reason: Core molecular function; correct. Supporting Evidence: PMID:1457827 The glp-1 gene encodes a membrane protein required for inductive cell interactions during development of the nematode Caenorhabditis elegans. PMID:1457827 10 epidermal growth factor [EGF]-like and 3 LNG repeats extracellularly and 6 cdc10/SWI6, or ankyrin, repeats intracellularly |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Ca2+-binding EGF-like repeats (IEA). Reason: Structural domain-level inference; not a signaling activity. Supporting Evidence: PMID:1457827 10 epidermal growth factor [EGF]-like and 3 LNG repeats extracellularly and 6 cdc10/SWI6, or ankyrin, repeats intracellularly |
| GO:0005634 nucleus | EXP PMID:9003776 Roles of the RAM and ANK domains in signaling by the C. eleg... | ACCEPT | Summary: Nuclear GLP-1 intracellular domain. Reason: The NICD acts in the nucleus with LAG-1. Supporting Evidence: PMID:9003776 First, we demonstrate that both ANK and RAM domains interact with the LAG-1 transcription factor. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nucleus (IEA from UniProt). Reason: Consistent with experimental data. Supporting Evidence: PMID:9003776 First, we demonstrate that both ANK and RAM domains interact with the LAG-1 transcription factor. |
| GO:0005737 cytoplasm | IDA PMID:15911573 EGO-1, a putative RNA-directed RNA polymerase, promotes germ... | KEEP AS NON CORE | Summary: Cytoplasmic GLP-1 immunostaining in germ cells. Reason: Intracellular GLP-1 most likely reflects biosynthetic and endocytic pools of a membrane receptor. It is not a site of GLP-1 function, but the experimental observation is not disputed. Supporting Evidence: PMID:15911573 In C. elegans, GLP-1/Notch signaling from the somatic gonad maintains a population of proliferating germ cells, while entry of germ cells into meiosis is triggered by the GLD-1 and GLD-2 pathways. |
| GO:0005737 cytoplasm | IDA PMID:9015263 Genes required for GLP-1 asymmetry in the early Caenorhabdit... | KEEP AS NON CORE | Summary: GLP-1 protein distribution in early embryos. Reason: As above: intracellular pools of a membrane receptor. Supporting Evidence: PMID:9015263 we have examined the distribution of GLP-1 protein in selected maternal effect mutants that affect pattern or fate in the early embryo |
| GO:0005886 plasma membrane | EXP PMID:7607081 lag-2 may encode a signaling ligand for the GLP-1 and LIN-12... | ACCEPT | Summary: GLP-1 at the plasma membrane of germ cells receiving LAG-2. Reason: Consistent with receptor function. Supporting Evidence: PMID:7607081 we propose that lag-2 may encode a signaling ligand for GLP-1/LIN-12 |
| GO:0005886 plasma membrane | IDA PMID:15911573 EGO-1, a putative RNA-directed RNA polymerase, promotes germ... | ACCEPT | Summary: Membrane-associated GLP-1 in germ cells. Reason: Correct. Supporting Evidence: PMID:15911573 In C. elegans, GLP-1/Notch signaling from the somatic gonad maintains a population of proliferating germ cells, while entry of germ cells into meiosis is triggered by the GLD-1 and GLD-2 pathways. |
| GO:0005886 plasma membrane | IDA PMID:7607080 GLP-1 is localized to the mitotic region of the C. elegans g... | ACCEPT | Summary: GLP-1 is tightly membrane-associated in mitotic germ cells. Reason: Direct evidence. Supporting Evidence: PMID:7607080 GLP-1 is tightly associated with membranes of mitotic germline cells, supporting its identification as an integral membrane protein. |
| GO:0005886 plasma membrane | IDA PMID:9015263 Genes required for GLP-1 asymmetry in the early Caenorhabdit... | ACCEPT | Summary: GLP-1 at blastomere membranes in the early embryo. Reason: Correct. Supporting Evidence: PMID:9015263 we have examined the distribution of GLP-1 protein in selected maternal effect mutants that affect pattern or fate in the early embryo |
| GO:0005886 plasma membrane | IDA PMID:9307971 Functional domains of LAG-2, a putative signaling ligand for... | ACCEPT | Summary: GLP-1 at the membrane of receiving cells in LAG-2 domain analysis. Reason: Consistent with receptor function; defer to curator. Supporting Evidence: PMID:9307971 The LAG-2 membrane protein is a putative signaling ligand for the LIN-12 and GLP-1 receptors of Caenorhabditis elegans. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane (IEA). Reason: Correct. Supporting Evidence: PMID:7607080 GLP-1 is tightly associated with membranes of mitotic germline cells, supporting its identification as an integral membrane protein. |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:32196486 GLP-1 Notch-LAG-1 CSL control of the germline stem cell fate... | ACCEPT | Summary: GLP-1/LAG-1 directly activates transcription of lst-1 and sygl-1 in the germline. Reason: Direct transcriptional role of the NICD-LAG-1 complex. Supporting Evidence: PMID:32196486 In the C. elegans germline, GLP-1 Notch signaling specifies the stem cell fate, employing the sequence-specific DNA binding protein LAG-1 to implement the transcriptional response. PMID:32196486 only lst-1 and sygl-1, the two known target genes of GLP-1 in the germline, fulfilled these criteria |
| GO:0007219 Notch signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: Notch signaling pathway (IEA). Reason: Correct for a Notch receptor. Supporting Evidence: PMID:1457827 The glp-1 gene encodes a membrane protein required for inductive cell interactions during development of the nematode Caenorhabditis elegans. |
| GO:0007349 cellularization | IMP PMID:19502484 MSP and GLP-1/Notch signaling coordinately regulate actomyos... | KEEP AS NON CORE | Summary: glp-1(rf) delays oocyte cellularization. Reason: Supported biological role that is a downstream output of GLP-1/Notch signaling rather than a core molecular activity. Supporting Evidence: PMID:19502484 glp-1 reduction-of-function mutants exhibit elevated rates of cytoplasmic streaming and delayed cellularization. |
| GO:0009880 embryonic pattern specification | IGI PMID:7585963 pop-1 encodes an HMG box protein required for the specificat... | KEEP AS NON CORE | Summary: GLP-1 is required for ABa/ABp fate asymmetry in the early embryo (IGI with pop-1). Reason: Supported biological role that is a downstream output of GLP-1/Notch signaling rather than a core molecular activity. Supporting Evidence: file:worm/glp-1/glp-1-uniprot.txt cell fates of the blastomeres, ABa and ABp |
| GO:0009880 embryonic pattern specification | IMP PMID:7585963 pop-1 encodes an HMG box protein required for the specificat... | KEEP AS NON CORE | Summary: GLP-1 is required for embryonic blastomere fate patterning. Reason: Supported biological role that is a downstream output of GLP-1/Notch signaling rather than a core molecular activity. Supporting Evidence: file:worm/glp-1/glp-1-uniprot.txt cell fates of the blastomeres, ABa and ABp |
| GO:0010468 regulation of gene expression | IGI PMID:15342467 ATX-2, the C. elegans ortholog of ataxin 2, functions in tra... | KEEP AS NON CORE | Summary: Genetic interaction with atx-2 affecting germline gene expression. Reason: Broad and indirect; GLP-1 regulates gene expression through LAG-1-dependent transcription of lst-1/sygl-1. Supporting Evidence: PMID:15342467 In the absence of ATX-2, proliferation of stem cells is reduced, and the germline is abnormally masculinized. |
| GO:0010468 regulation of gene expression | IGI PMID:15342467 ATX-2, the C. elegans ortholog of ataxin 2, functions in tra... | KEEP AS NON CORE | Summary: Genetic interaction affecting germline gene expression. Reason: As above. Supporting Evidence: PMID:15342467 In the absence of ATX-2, proliferation of stem cells is reduced, and the germline is abnormally masculinized. |
| GO:0010608 post-transcriptional regulation of gene expression | IMP PMID:32196486 GLP-1 Notch-LAG-1 CSL control of the germline stem cell fate... | MARK AS OVER ANNOTATED | Summary: glp-1-dependent FBF-2 protein accumulation. Reason: GLP-1 acts transcriptionally. The post-transcriptional effects are mediated by its targets LST-1 and SYGL-1 acting with FBF, so GLP-1 does not itself perform post-transcriptional regulation. Supporting Evidence: PMID:32196486 our analysis also suggests that the function of the primary response genes lst-1 and sygl-1 can account for the glp-1 dependent peak protein accumulation of FBF-2 |
| GO:0010628 positive regulation of gene expression | IMP PMID:26963674 A 44 bp intestine-specific hermaphrodite-specific enhancer f... | MARK AS OVER ANNOTATED | Summary: Loss of germline (glp-1) affects intestinal vit-2 enhancer activity. Reason: This is an indirect, systemic effect of germline presence on intestinal vitellogenin transcription, not a GLP-1 activity. Supporting Evidence: PMID:26963674 indirectly regulated by the germline, by daf-2/insulin signaling |
| GO:0012505 endomembrane system | IDA PMID:7607080 GLP-1 is localized to the mitotic region of the C. elegans g... | KEEP AS NON CORE | Summary: GLP-1 immunostaining on internal membranes. Reason: Reflects receptor trafficking; not a functional location. Supporting Evidence: PMID:7607080 GLP-1 is tightly associated with membranes of mitotic germline cells, supporting its identification as an integral membrane protein. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Membrane (IEA). Reason: Correct but general. Supporting Evidence: PMID:7607080 GLP-1 is tightly associated with membranes of mitotic germline cells, supporting its identification as an integral membrane protein. |
| GO:0016328 lateral plasma membrane | IDA PMID:7607080 GLP-1 is localized to the mitotic region of the C. elegans g... | ACCEPT | Summary: GLP-1 on germ-cell membranes of the distal mitotic region. Reason: Direct immunolocalization; defer to curator on the lateral membrane assignment. Supporting Evidence: PMID:7607080 GLP-1 is tightly associated with membranes of mitotic germline cells, supporting its identification as an integral membrane protein. |
| GO:0022611 dormancy process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Dormancy process (ARBA IEA). Reason: GLP-1 in neurons maintains the dauer state. Non-core. Supporting Evidence: PMID:18599512 we demonstrate that glp-1, one of the two C. elegans Notch receptors, and its ligand lag-2 are expressed in neurons during the dauer stage, and both genes are required to maintain this stage in a daf-7/TGFbeta dauer constitutive background |
| GO:0030154 cell differentiation | IEA GO_REF:0000002 | ACCEPT | Summary: Cell differentiation (IEA). Reason: General but correct. Supporting Evidence: PMID:32196486 In the C. elegans germline, GLP-1 Notch signaling specifies the stem cell fate, employing the sequence-specific DNA binding protein LAG-1 to implement the transcriptional response. |
| GO:0030424 axon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: GLP-1 localized to axons during dauer. Reason: Neuronal expression during dauer; non-core location. Supporting Evidence: PMID:18599512 we demonstrate that glp-1, one of the two C. elegans Notch receptors, and its ligand lag-2 are expressed in neurons during the dauer stage, and both genes are required to maintain this stage in a daf-7/TGFbeta dauer constitutive background |
| GO:0040024 dauer larval development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Dauer larval development (ARBA IEA). Reason: Supported biological role that is a downstream output of GLP-1/Notch signaling rather than a core molecular activity. Supporting Evidence: PMID:18599512 we demonstrate that glp-1, one of the two C. elegans Notch receptors, and its ligand lag-2 are expressed in neurons during the dauer stage, and both genes are required to maintain this stage in a daf-7/TGFbeta dauer constitutive background |
| GO:0043055 maintenance of dauer | IGI PMID:18599512 Notch signalling is required for both dauer maintenance and ... | KEEP AS NON CORE | Summary: glp-1 and lag-2 are required to maintain dauer. Reason: Supported biological role that is a downstream output of GLP-1/Notch signaling rather than a core molecular activity. Supporting Evidence: PMID:18599512 we demonstrate that glp-1, one of the two C. elegans Notch receptors, and its ligand lag-2 are expressed in neurons during the dauer stage, and both genes are required to maintain this stage in a daf-7/TGFbeta dauer constitutive background |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:9003776 Roles of the RAM and ANK domains in signaling by the C. eleg... | ACCEPT | Summary: GLP-1 ANK repeats activate transcription. Reason: Consistent with the NICD coactivator role; GLP-1-dependent transcription of lst-1/sygl-1 in vivo. Supporting Evidence: PMID:9003776 Finally, we show in yeast that the ANK repeats are strong transcriptional activators. PMID:32196486 In the C. elegans germline, GLP-1 Notch signaling specifies the stem cell fate, employing the sequence-specific DNA binding protein LAG-1 to implement the transcriptional response. |
| GO:0048589 developmental growth | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Developmental growth (ARBA IEA). Reason: Broad; reflects germline proliferation and oocyte growth phenotypes. Supporting Evidence: PMID:19502484 we show that GLP-1/Notch signaling functions in the germline to modulate oocyte growth when sperm are available for fertilization and the major sperm protein (MSP) hormone is present. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IEA GO_REF:0000117 | ACCEPT | Summary: Binding of the CSL transcription factor LAG-1 (ARBA IEA). Reason: Consistent with experimental data. Supporting Evidence: PMID:9003776 First, we demonstrate that both ANK and RAM domains interact with the LAG-1 transcription factor. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:9003776 Roles of the RAM and ANK domains in signaling by the C. eleg... | ACCEPT | Summary: The GLP-1 RAM domain directly binds LAG-1. Reason: Direct binding to a DNA-binding transcription factor. Supporting Evidence: PMID:9003776 the interaction between the RAM domain and LAG-1 is likely to be direct, since it is observed by co-precipitation of the proteins in vitro as well as by yeast two-hybrid experiments |
| GO:0090575 RNA polymerase II transcription regulator complex | IDA PMID:10830967 LAG-3 is a putative transcriptional activator in the C. eleg... | ACCEPT | Summary: The NICD forms a ternary complex with LAG-1 and LAG-3. Reason: Direct biochemical evidence. Supporting Evidence: PMID:10830967 Here we identify LAG-3, a glutamine-rich protein that forms a ternary complex together with the LAG-1 DNA-binding protein and the receptor's intracellular domain. |
| GO:0090575 RNA polymerase II transcription regulator complex | IEA GO_REF:0000117 | ACCEPT | Summary: RNA polymerase II transcription regulator complex (ARBA IEA). Reason: Correct. Supporting Evidence: PMID:10830967 Here we identify LAG-3, a glutamine-rich protein that forms a ternary complex together with the LAG-1 DNA-binding protein and the receptor's intracellular domain. |
| GO:0099636 cytoplasmic streaming | IMP PMID:19502484 MSP and GLP-1/Notch signaling coordinately regulate actomyos... | KEEP AS NON CORE | Summary: glp-1(rf) elevates oocyte cytoplasmic streaming. Reason: Supported biological role that is a downstream output of GLP-1/Notch signaling rather than a core molecular activity. Supporting Evidence: PMID:19502484 glp-1 reduction-of-function mutants exhibit elevated rates of cytoplasmic streaming and delayed cellularization. |
| GO:0160096 nematode pharyngeal muscle development | IGI PMID:7585963 pop-1 encodes an HMG box protein required for the specificat... | KEEP AS NON CORE | Summary: GLP-1 is required for induction of anterior pharynx from ABa descendants (IGI). Reason: Supported biological role that is a downstream output of GLP-1/Notch signaling rather than a core molecular activity. Supporting Evidence: file:worm/glp-1/glp-1-uniprot.txt signaling by glp-1 induces ABa descendants to produce anterior |
| GO:0160096 nematode pharyngeal muscle development | IMP PMID:7585963 pop-1 encodes an HMG box protein required for the specificat... | KEEP AS NON CORE | Summary: GLP-1 is required for anterior pharynx induction (IMP). Reason: Supported biological role that is a downstream output of GLP-1/Notch signaling rather than a core molecular activity. Supporting Evidence: file:worm/glp-1/glp-1-uniprot.txt signaling by glp-1 induces ABa descendants to produce anterior |
| GO:1905936 regulation of germ cell proliferation | IGI PMID:25552605 hecd-1 modulates notch activity in Caenorhabditis elegans. | ACCEPT | Summary: hecd-1 negatively modulates glp-1 activity in germ-cell proliferation. Reason: Maintenance of the germline stem cell pool is the best-characterized GLP-1 function: GLP-1 in germ cells receives the LAG-2/APX-1 signal from the distal tip cell niche and, via LAG-1, activates sygl-1 and lst-1 to keep cells in the proliferative stem cell state. Supporting Evidence: PMID:25552605 but acts autonomously as a negative modulator of glp-1/Notch activity in the germ line PMID:15911573 In C. elegans, GLP-1/Notch signaling from the somatic gonad maintains a population of proliferating germ cells, while entry of germ cells into meiosis is triggered by the GLD-1 and GLD-2 pathways. |
| GO:1905938 positive regulation of germ cell proliferation | IMP PMID:25552605 hecd-1 modulates notch activity in Caenorhabditis elegans. | ACCEPT | Summary: GLP-1 positively regulates germ cell proliferation. Reason: Maintenance of the germline stem cell pool is the best-characterized GLP-1 function: GLP-1 in germ cells receives the LAG-2/APX-1 signal from the distal tip cell niche and, via LAG-1, activates sygl-1 and lst-1 to keep cells in the proliferative stem cell state. Supporting Evidence: PMID:15911573 In C. elegans, GLP-1/Notch signaling from the somatic gonad maintains a population of proliferating germ cells, while entry of germ cells into meiosis is triggered by the GLD-1 and GLD-2 pathways. PMID:3677168 Mutations in glp-1 cause germ cells that would normally divide mitotically to enter meiosis. |
| GO:2000648 positive regulation of stem cell proliferation | IMP PMID:3677168 glp-1 is required in the germ line for regulation of the dec... | ACCEPT | Summary: GLP-1 is required in the germ line to keep cells mitotic. Reason: Maintenance of the germline stem cell pool is the best-characterized GLP-1 function: GLP-1 in germ cells receives the LAG-2/APX-1 signal from the distal tip cell niche and, via LAG-1, activates sygl-1 and lst-1 to keep cells in the proliferative stem cell state. Supporting Evidence: PMID:3677168 Mutations in glp-1 cause germ cells that would normally divide mitotically to enter meiosis. PMID:3677168 We propose that glp-1 acts as part of the receiving mechanism in the interaction between the distal tip cell and germ line. |
| GO:2000737 negative regulation of stem cell differentiation | IMP PMID:26552888 DAF-18/PTEN locally antagonizes insulin signalling to couple... | ACCEPT | Summary: Loss of glp-1 drives germline stem cells to differentiate. Reason: Maintenance of the germline stem cell pool is the best-characterized GLP-1 function: GLP-1 in germ cells receives the LAG-2/APX-1 signal from the distal tip cell niche and, via LAG-1, activates sygl-1 and lst-1 to keep cells in the proliferative stem cell state. Supporting Evidence: PMID:26552888 using a conditional loss-of-function allele in the Notch receptor ( glp-1 ) PMID:32196486 In the C. elegans germline, GLP-1 Notch signaling specifies the stem cell fate, employing the sequence-specific DNA binding protein LAG-1 to implement the transcriptional response. |
| GO:1990433 CSL-Notch-Mastermind transcription factor complex | IDA PMID:10830967 LAG-3 is a putative transcriptional activator in the C. eleg... | NEW | Summary: The GLP-1 intracellular domain forms a ternary complex with LAG-1 (CSL) and LAG-3 (Mastermind-like). Reason: Direct biochemical evidence (yeast and in vitro) for the GLP-1 NICD in the CSL-Notch-Mastermind complex, which parallels the LIN-12 annotation to this complex. Receptor ankyrin-repeat mutants that abolish signaling cannot form the complex. Supporting Evidence: PMID:10830967 Here we identify LAG-3, a glutamine-rich protein that forms a ternary complex together with the LAG-1 DNA-binding protein and the receptor's intracellular domain. PMID:10830967 Receptors with mutant ankyrin repeats that abrogate signal transduction are incapable of complex formation both in yeast and in vitro. |
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Download this section (compressed HTML)Q: GLP-1 is placed in PANTHER PTHR45836:SF23 (Notch homolog 1) while its paralog LIN-12 is placed in PTHR24049:SF22 (crumbs homolog). Should both C. elegans Notch receptors share a Notch receptor subfamily and its IBA annotations?
Q: Are lst-1 and sygl-1 truly the only primary germline GLP-1/LAG-1 targets, and which GLP-1 somatic (dauer neuron, embryonic) targets are direct?
Experiment: Use endogenously tagged GLP-1 NICD with auxin-inducible degradation to map the dauer-neuron transcriptional targets and test whether they share LAG-1 binding sites.
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