id: Q23536 gene_symbol: lgg-2 product_type: PROTEIN status: DRAFT taxon: id: NCBITaxon:6239 label: Caenorhabditis elegans description: LGG-2 is an LC3-type ATG8 family protein that functions as a ubiquitin-like modifier in autophagy in C. elegans. Unlike its paralog LGG-1 (GABARAP-type), LGG-2 acts downstream in the autophagy pathway, primarily promoting autophagosome maturation and autophagosome-lysosome fusion through direct interaction with the HOPS complex subunit VPS-39. LGG-2 is lipidated (conjugated to phosphatidylethanolamine) at its C-terminal glycine residue, which is essential for membrane association and autophagosome localization. LGG-2 recognizes LIR (LC3-interacting region) motifs in cargo receptors such as SQST-1 and SEPA-1. The protein plays roles in multiple selective autophagy pathways including aggrephagy (degradation of protein aggregates), allophagy (degradation of paternal mitochondria during fertilization), xenophagy (degradation of bacterial toxins), and contributes to apoptotic corpse clearance by facilitating autophagosome-phagosome fusion. LGG-1 and LGG-2 have partially overlapping but distinct functions, with LGG-1 acting upstream to allow LGG-2 localization to autophagosomes, and LGG-2 acting downstream to promote degradation steps. existing_annotations: - term: id: GO:0000045 label: autophagosome assembly evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: LGG-2 is recruited to nascent autophagosomes and plays a role in autophagosome biogenesis, though its primary function is downstream in maturation rather than initial assembly. The IBA annotation is phylogenetically sound as ATG8 family members are conserved in this function (PMID:24374177). action: ACCEPT reason: ATG8 family proteins including LGG-2 are conjugated to autophagosomal membranes during autophagosome formation. While LGG-2 functions primarily downstream in maturation, it is still involved in the autophagosome assembly process as demonstrated by its localization to autophagosomes and requirement for autophagic flux. The IBA annotation based on phylogeny is appropriate. supported_by: - reference_id: PMID:24374177 supporting_text: The formation of the autophagic vesicles requires the recruitment of ubiquitin-like Atg8 proteins to the membrane of nascent autophagosomes. - reference_id: PMID:20523114 supporting_text: The formation of the autophagic vesicles requires the recruitment of the Atg8 ubiquitin-like proteins to the membrane of the nascent autophagosomes. - term: id: GO:0000421 label: autophagosome membrane evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: LGG-2 localizes to autophagosome membranes, where it is conjugated to phosphatidylethanolamine (PE). This localization is well-established experimentally (PMID:24374177, PMID:20523114). action: ACCEPT reason: Multiple studies demonstrate LGG-2 localizes to autophagosome membranes in a lipidation-dependent manner. The G130A mutant that cannot be lipidated shows diffuse cytoplasmic localization instead of punctate autophagosomal pattern. supported_by: - reference_id: PMID:24374177 supporting_text: Both LGG-1 and LGG-2 localize to the autophagosomes but display partially overlapping patterns. - reference_id: PMID:20523114 supporting_text: The C-terminal glycine residue of LGG-2 is essential for post-translational modification and localization to the autophagosomes. - term: id: GO:0000423 label: mitophagy evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: LGG-2 participates in allophagy, the autophagic degradation of paternal mitochondria after fertilization. This represents a developmentally programmed form of mitophagy in C. elegans (PMID:24374177, PMID:25126728). action: ACCEPT reason: The IBA annotation for mitophagy is supported by direct experimental evidence for LGG-2 function in allophagy (degradation of paternal mitochondria during fertilization). LGG-2 is required for degradation of LGG-1-positive allophagic autophagosomes containing paternal organelles. supported_by: - reference_id: PMID:24374177 supporting_text: During allophagy, a developmentally stereotyped autophagic flux, LGG-1 acts upstream of LGG-2 to allow its localization to autophagosomes. - reference_id: UniProt:Q23536 supporting_text: Involved in allophagy, which is an autophagic process in which paternal mitochondria and organelles are degraded during fertilization - term: id: GO:0008429 label: phosphatidylethanolamine binding evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: LGG-2 is covalently conjugated to phosphatidylethanolamine (PE) at its C-terminal glycine residue through the ATG7-ATG3 lipidation machinery, which is essential for membrane association (PMID:26687600). action: ACCEPT reason: ATG8 family proteins including LGG-2 are lipidated by conjugation to PE. The G130 residue at the C-terminus is the lipidation site. Mutation of G130A abolishes membrane puncta formation, demonstrating the functional importance of PE conjugation. supported_by: - reference_id: PMID:26687600 supporting_text: Lipidated LGG-1 and LGG-2 possess distinct membrane tethering and fusion activities - reference_id: file:worm/lgg-2/lgg-2-deep-research-falcon.md supporting_text: LGG-2 is synthesized as a precursor, cleaved to expose a C-terminal glycine, and conjugated to phosphatidylethanolamine (PE) by the ATG7-ATG3 machinery - term: id: GO:0097352 label: autophagosome maturation evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: This is a core function of LGG-2. LGG-2 controls autophagosome maturation and facilitates tethering with lysosomes through interaction with VPS-39 of the HOPS complex (PMID:24374177). action: ACCEPT reason: Autophagosome maturation is the primary distinguishing function of LGG-2 compared to LGG-1. LGG-2 acts downstream of LGG-1 to promote maturation and fusion with lysosomes. This is strongly supported by experimental evidence showing LGG-2 interaction with VPS-39/HOPS complex. supported_by: - reference_id: PMID:24374177 supporting_text: LGG-2 controls the maturation of LGG-1-positive autophagosomes and facilitates the tethering with the lysosomes through a direct interaction with the VPS-39 HOPS complex subunit. - term: id: GO:0031625 label: ubiquitin protein ligase binding evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: LGG-2 interacts with ATG-7 and ATG-3, which are E1-like and E2-like enzymes in the ubiquitin-like conjugation system that mediates LGG-2 lipidation (PMID:26687600). action: ACCEPT reason: ATG8 proteins interact with the ATG7/ATG3 conjugation machinery which has structural similarity to ubiquitin ligases. LGG-2 directly interacts with ATG-7 and ATG-3 for its lipidation, supporting this annotation. supported_by: - reference_id: PMID:26687600 supporting_text: LGG-1 and LGG-2 interact differentially with autophagy substrates and Atg proteins, many of which carry a LIR motif - term: id: GO:0006995 label: cellular response to nitrogen starvation evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: Autophagy is induced by starvation conditions including nitrogen starvation. LGG-2 localization is modified during starvation when autophagy is induced (PMID:20523114). action: ACCEPT reason: As an essential autophagy factor, LGG-2 participates in the autophagic response to starvation. The IBA annotation based on ATG8 family conservation is appropriate given the universal role of autophagy in nutrient stress response. supported_by: - reference_id: PMID:20523114 supporting_text: We also demonstrate that the localization of both proteins is modified in several physiological processes when autophagy is induced, namely during diapause "dauer" larval formation, starvation and aging - term: id: GO:0008017 label: microtubule binding evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: This annotation is transferred from mammalian LC3/MAP1LC3 proteins which were originally identified as microtubule-associated protein light chains. However, the microtubule binding function is not the primary or well-characterized function for C. elegans LGG-2. action: MARK_AS_OVER_ANNOTATED reason: While mammalian LC3 proteins were named for their association with microtubule-associated proteins, the primary characterized function of LGG-2 in C. elegans is in autophagy, not microtubule binding. There is no direct experimental evidence for LGG-2 microtubule binding in C. elegans. This annotation represents a potential over-extension of the mammalian LC3 nomenclature history rather than a demonstrated function. additional_reference_ids: - PMID:24374177 - PMID:20523114 - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000044 review: summary: LGG-2 has diffuse cytoplasmic localization in addition to punctate autophagosomal localization (PMID:24374177). action: ACCEPT reason: IEA annotation based on UniProt subcellular location is consistent with experimental observations showing cytoplasmic distribution of LGG-2, particularly the unlipidated form. supported_by: - reference_id: PMID:24374177 supporting_text: Both LGG-1 and LGG-2 localize to the autophagosomes but display partially overlapping patterns - term: id: GO:0005776 label: autophagosome evidence_type: IEA original_reference_id: GO_REF:0000120 review: summary: LGG-2 localizes to autophagosomes when lipidated, forming punctate structures visible by fluorescence microscopy (PMID:24374177, PMID:20523114). action: ACCEPT reason: Strong experimental evidence supports LGG-2 localization to autophagosomes. The IEA annotation is consistent with multiple IDA-level observations. supported_by: - reference_id: PMID:24374177 supporting_text: Both LGG-1 and LGG-2 localize to the autophagosomes but display partially overlapping patterns - reference_id: PMID:20523114 supporting_text: The C-terminal glycine residue of LGG-2 is essential for post-translational modification and localization to the autophagosomes - term: id: GO:0005886 label: plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000044 review: summary: UniProt indicates cell membrane localization based on the lipid anchor. However, the primary localization is to autophagosomal membranes, not the plasma membrane per se. action: MARK_AS_OVER_ANNOTATED reason: While LGG-2 is lipid-anchored via PE conjugation, its functional localization is to autophagosomal membranes, not the plasma membrane. The plasma membrane annotation may be an artifact of the lipid-anchor keyword mapping. Experimental studies consistently show autophagosomal, not plasma membrane, localization. supported_by: - reference_id: PMID:24374177 supporting_text: Both LGG-1 and LGG-2 localize to the autophagosomes but display partially overlapping patterns - term: id: GO:0006914 label: autophagy evidence_type: IEA original_reference_id: GO_REF:0000043 review: summary: LGG-2 is a core autophagy factor, essential for autophagic flux and autophagosome maturation (PMID:24374177, PMID:20523114). action: ACCEPT reason: This is a core function. LGG-2 is an ATG8 family protein essential for autophagy. The IEA annotation based on UniProt keyword is well-supported by extensive experimental evidence. supported_by: - reference_id: PMID:24374177 supporting_text: The formation of the autophagic vesicles requires the recruitment of ubiquitin-like Atg8 proteins to the membrane of nascent autophagosomes. - term: id: GO:0006950 label: response to stress evidence_type: IEA original_reference_id: GO_REF:0000117 review: summary: Autophagy is a stress response pathway. LGG-2 participates in autophagy induced by various stresses including starvation, pathogen infection, and toxic substances (PMID:20523114, PMID:27875098). action: ACCEPT reason: This broad annotation is appropriate given LGG-2's role in autophagy, which is a key cellular stress response mechanism. Evidence shows LGG-2 function in response to starvation, aging, and pathogen-derived toxins. supported_by: - reference_id: PMID:20523114 supporting_text: We also demonstrate that the localization of both proteins is modified in several physiological processes when autophagy is induced, namely during diapause "dauer" larval formation, starvation and aging - term: id: GO:0016236 label: macroautophagy evidence_type: IEA original_reference_id: GO_REF:0000117 review: summary: LGG-2 functions in macroautophagy (canonical autophagy involving double-membrane autophagosome formation), as opposed to other forms of autophagy (PMID:24374177). action: ACCEPT reason: LGG-2 is specifically involved in macroautophagy, the double-membrane autophagosome-dependent pathway. This is its core function as an ATG8 family protein that decorates autophagosomal membranes. supported_by: - reference_id: PMID:24374177 supporting_text: Both LGG-1 and LGG-2 localize to the autophagosomes but display partially overlapping patterns. - term: id: GO:0031410 label: cytoplasmic vesicle evidence_type: IEA original_reference_id: GO_REF:0000043 review: summary: LGG-2 localizes to autophagosomes, which are cytoplasmic vesicles. This is a broad parent term of autophagosome. action: ACCEPT reason: As an autophagosomal protein, LGG-2 localizes to cytoplasmic vesicles (specifically autophagosomes). This annotation is technically correct though less specific than the autophagosome annotation. supported_by: - reference_id: PMID:24374177 supporting_text: Both LGG-1 and LGG-2 localize to the autophagosomes but display partially overlapping patterns. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14704431 review: summary: High-throughput Y2H interactome study identified LGG-2 protein-protein interactions (PMID:14704431). action: MODIFY reason: The generic "protein binding" term provides little information about LGG-2's actual molecular function. LGG-2 has specific binding functions including LIR motif binding in cargo receptors and interaction with the ATG conjugation machinery. However, the Y2H study identified interaction with ATG-4.1 (atg-4.1), which is the protease that processes ATG8 proteins. A more informative term would be specific to the interaction. proposed_replacement_terms: - id: GO:0031625 label: ubiquitin protein ligase binding supported_by: - reference_id: PMID:14704431 supporting_text: Starting with a subset of metazoan-specific proteins, more than 4000 interactions were identified from high-throughput, yeast two-hybrid (HT=Y2H) screens. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19123269 review: summary: Follow-up high-throughput Y2H interactome study confirmed LGG-2 interactions (PMID:19123269). action: MODIFY reason: Same as above - generic protein binding term is uninformative. The interaction with ATG-4.1 is specific and could be annotated with a more specific term if available. proposed_replacement_terms: - id: GO:0031625 label: ubiquitin protein ligase binding supported_by: - reference_id: PMID:19123269 supporting_text: "We present an expanded Caenorhabditis elegans protein-protein interaction network, or \"interactome\" map derived from testing a matrix of ~ 10,000 × ~ 10,000 proteins using a highly specific high-throughput yeast two-hybrid system" - term: id: GO:0097237 label: cellular response to toxic substance evidence_type: IMP original_reference_id: PMID:27875098 review: summary: LGG-2 is required for autophagy-mediated defense against the bacterial pore-forming toxin Cry5B. RNAi knockdown of lgg-2 reduces autophagic degradation of membrane pore-forming toxin (PMID:27875098). action: ACCEPT reason: Strong experimental evidence shows lgg-2 is required for tolerance to bacterial pore-forming toxin intoxication. This is mediated through autophagy-dependent degradation of the toxin. supported_by: - reference_id: PMID:27875098 supporting_text: autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously in the PFT-targeted intestinal cells in C. elegans - reference_id: UniProt:Q23536 supporting_text: RNAi-mediated knockdown reduces autophagic degradation of membrane pore-forming toxin Cry5B. - term: id: GO:0001778 label: plasma membrane repair evidence_type: IMP original_reference_id: PMID:27875098 review: summary: LGG-2/autophagy contributes to repair of plasma membrane pores caused by bacterial pore-forming toxins (PMID:27875098). action: KEEP_AS_NON_CORE reason: While the annotation is experimentally supported, plasma membrane repair is not the core molecular function of LGG-2 - it is a downstream phenotypic consequence of autophagy activity in response to pore-forming toxin damage. The primary function is in autophagy/xenophagy, with membrane repair being a secondary outcome. supported_by: - reference_id: PMID:27875098 supporting_text: autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT and repair of membrane-pore cell-autonomously - reference_id: UniProt:Q23536 supporting_text: Also plays a role in membrane-pore repair - term: id: GO:0098792 label: xenophagy evidence_type: IMP original_reference_id: PMID:27875098 review: summary: LGG-2 is required for xenophagic degradation of bacterial pore-forming toxin (PFT) Cry5B (PMID:27875098). action: ACCEPT reason: Strong experimental evidence from PMID:27875098 demonstrates that LGG-2 functions in xenophagy to degrade bacterial toxins. This is a specific selective autophagy pathway consistent with LGG-2's role as an ATG8 family autophagy factor. supported_by: - reference_id: PMID:27875098 supporting_text: autophagy controls the susceptibility of animals to PFT toxicity through xenophagic degradation of PFT - reference_id: UniProt:Q23536 supporting_text: Involved in xenophagy, the autophagy-mediated degradation of pathogens and pathogen products, such as toxins - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24374177 review: summary: LGG-2 interacts with VPS-39, a subunit of the HOPS tethering complex (PMID:24374177). This interaction mediates autophagosome-lysosome fusion. action: MODIFY reason: The interaction with VPS-39 should be captured with a more specific term than generic protein binding. This interaction is functionally important for autophagosome-lysosome tethering and fusion. proposed_replacement_terms: - id: GO:0031593 label: SNARE complex assembly additional_reference_ids: - PMID:24374177 supported_by: - reference_id: PMID:24374177 supporting_text: LGG-2 controls the maturation of LGG-1-positive autophagosomes and facilitates the tethering with the lysosomes through a direct interaction with the VPS-39 HOPS complex subunit. - term: id: GO:1901098 label: positive regulation of autophagosome maturation evidence_type: IMP original_reference_id: PMID:24374177 review: summary: This is a core function of LGG-2. LGG-2 positively regulates autophagosome maturation through interaction with VPS-39/HOPS complex (PMID:24374177). action: ACCEPT reason: This accurately captures LGG-2's primary distinguishing function - promoting autophagosome maturation and fusion with lysosomes. lgg-2 mutants show defective autophagosome degradation with accumulation of LGG-1-positive autophagosomes. supported_by: - reference_id: PMID:24374177 supporting_text: LGG-2 controls the maturation of LGG-1-positive autophagosomes and facilitates the tethering with the lysosomes through a direct interaction with the VPS-39 HOPS complex subunit. - reference_id: UniProt:Q23536 supporting_text: Lysosomes have a reduced capacity to interact with autophagosomes in embryos and furthermore, there is defective autophagosome degradation with an accumulation of lgg-1-positive autophagosomes in 500-cell embryos - term: id: GO:0050830 label: defense response to Gram-positive bacterium evidence_type: IEP original_reference_id: PMID:24882217 review: summary: lgg-2 expression is upregulated during S. aureus infection as part of HLH-30/TFEB-mediated host defense response (PMID:24882217). action: KEEP_AS_NON_CORE reason: The IEP evidence indicates lgg-2 expression changes during infection, but this reflects autophagy induction as a general host defense mechanism rather than a specific anti-Gram-positive function. The annotation is valid but represents a downstream consequence of autophagy induction by infection, not a core molecular function. supported_by: - reference_id: PMID:24882217 supporting_text: HLH-30 was activated shortly after Staphylococcus aureus infection, and drove the expression of close to 80% of the host response, including antimicrobial and autophagy genes that were essential for host tolerance of infection. - term: id: GO:0000421 label: autophagosome membrane evidence_type: IDA original_reference_id: PMID:24374177 review: summary: Direct experimental evidence shows LGG-2 localizes to autophagosome membranes, forming punctate structures in embryos (PMID:24374177). action: ACCEPT reason: IDA evidence directly demonstrates LGG-2 localization to autophagosome membranes through fluorescent reporter imaging. Localization requires ATG-7-dependent lipidation. supported_by: - reference_id: PMID:24374177 supporting_text: Both LGG-1 and LGG-2 localize to the autophagosomes but display partially overlapping patterns. - reference_id: PMID:24374177 supporting_text: LGG-1 acts upstream of LGG-2 to allow its localization to autophagosomes. - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:20523114 review: summary: LGG-2 shows cytoplasmic localization in addition to autophagosomal puncta (PMID:20523114). action: ACCEPT reason: IDA evidence confirms cytoplasmic localization of LGG-2, particularly the non-lipidated pool. supported_by: - reference_id: PMID:20523114 supporting_text: During C. elegans development the two proteins share a similar expression pattern and localization but LGG-2 is more abundant in the neurons. - term: id: GO:0061909 label: autophagosome-lysosome fusion evidence_type: IMP original_reference_id: PMID:24374177 review: summary: LGG-2 promotes autophagosome-lysosome fusion through interaction with VPS-39 of the HOPS tethering complex. This is a core function that distinguishes LGG-2 from LGG-1 (PMID:24374177). action: NEW reason: This term precisely captures LGG-2's primary molecular role in promoting autophagosome-lysosome fusion. The evidence shows LGG-2 interacts with VPS-39/HOPS to tether autophagosomes to lysosomes. supported_by: - reference_id: PMID:24374177 supporting_text: Genetic analyses sustain a sequential implication of LGG-1, LGG-2, RAB-7, and HOPS complex to generate autolysosomes. - reference_id: PMID:24374177 supporting_text: LGG-2 controls the maturation of LGG-1-positive autophagosomes and facilitates the tethering with the lysosomes through a direct interaction with the VPS-39 HOPS complex subunit. references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: - statement: IBA annotations for ATG8 family functions based on phylogenetic conservation - id: GO_REF:0000043 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:14704431 title: A map of the interactome network of the metazoan C. elegans. findings: - statement: High-throughput Y2H identified LGG-2 protein interactions including ATG-4.1 supporting_text: A map of the interactome network of the metazoan C. elegans. - id: PMID:19123269 title: Empirically controlled mapping of the Caenorhabditis elegans protein-protein interactome network. findings: - statement: Expanded worm interactome map confirming LGG-2 interactions supporting_text: Empirically controlled mapping of the Caenorhabditis elegans protein-protein interactome network. - id: PMID:20523114 title: The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans. findings: - statement: LGG-2 is more closely related to human LC3 than LGG-1 supporting_text: The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans. - statement: LGG-2 C-terminal glycine essential for lipidation and autophagosome localization supporting_text: The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans. - statement: LGG-2 and LGG-1 act synergistically in dauer formation and longevity supporting_text: The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans. - statement: LGG-2 localization modified during starvation and aging when autophagy induced supporting_text: The autophagosomal protein LGG-2 acts synergistically with LGG-1 in dauer formation and longevity in C. elegans. - id: PMID:24374177 title: The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by interacting with the HOPS subunit VPS39. findings: - statement: LGG-1 acts upstream of LGG-2 during allophagy supporting_text: The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by interacting with the HOPS subunit VPS39. - statement: LGG-2 controls autophagosome maturation through direct interaction with VPS-39 supporting_text: The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by interacting with the HOPS subunit VPS39. - statement: LGG-2 facilitates autophagosome-lysosome tethering via HOPS complex supporting_text: The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by interacting with the HOPS subunit VPS39. - statement: Sequential pathway LGG-1 -> LGG-2 -> RAB-7 -> HOPS for autolysosome formation supporting_text: The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by interacting with the HOPS subunit VPS39. - statement: G130A mutation abolishes autophagosome localization supporting_text: The C. elegans LC3 acts downstream of GABARAP to degrade autophagosomes by interacting with the HOPS subunit VPS39. - id: PMID:24882217 title: Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. findings: - statement: HLH-30/TFEB drives expression of autophagy genes including lgg-2 during S. aureus infection supporting_text: Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. - statement: Autophagy genes essential for host tolerance of infection supporting_text: Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. - id: PMID:27875098 title: HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans. findings: - statement: LGG-2 required for xenophagic degradation of bacterial pore-forming toxin Cry5B supporting_text: HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans. - statement: Autophagy-dependent membrane pore repair supporting_text: HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans. - statement: lgg-2 RNAi reduces autophagic degradation of PFT supporting_text: HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans. - id: PMID:26687600 title: Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy. findings: - statement: Crystal structure of LGG-2 with LIR peptide binding supporting_text: Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy. - statement: LGG-2 recognizes LIR motifs in cargo receptors SQST-1, SEPA-1, EPG-2 supporting_text: Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy. - statement: LGG-2 interacts with ATG-7, ATG-3 for lipidation supporting_text: Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy. - statement: LGG-2 interacts with ATG-16.1 and ATG-16.2 WD domains supporting_text: Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy. - statement: LGG-2 less effective at promoting membrane fusion than LGG-1 supporting_text: Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy. core_functions: - molecular_function: id: GO:0008429 label: phosphatidylethanolamine binding description: LGG-2 is conjugated to phosphatidylethanolamine (PE) at its C-terminal glycine (G130) through the ATG7-ATG3 lipidation machinery. This modification is essential for membrane association and autophagosome localization. supported_by: - reference_id: PMID:26687600 supporting_text: This protein is subject to lipidation. full_text_unavailable: true - reference_id: PMID:24374177 supporting_text: 'G->A [at position 130]: Diffuse cytosolic localization in 500-cell embryos with no punctate pattern' full_text_unavailable: true directly_involved_in: - id: GO:0097352 label: autophagosome maturation - id: GO:0061909 label: autophagosome-lysosome fusion locations: - id: GO:0000421 label: autophagosome membrane suggested_questions: - question: What is the functional significance of distinct LGG-1 and LGG-2 positive autophagosome populations during development and stress conditions? - question: Does LGG-2 have cargo-specific functions distinct from LGG-1 beyond the autophagosome maturation step? - question: What regulates the sequential handoff from LGG-1 to LGG-2 on autophagosomes? suggested_experiments: - description: Proteomics to identify LGG-2-specific cargo receptors and interaction partners distinct from LGG-1. - description: Live imaging with dual LGG-1/LGG-2 reporters to characterize the temporal dynamics of ATG8 protein exchange on individual autophagosomes. - description: Structure-function analysis of LGG-2 domains required for VPS-39 interaction and autophagosome-lysosome fusion. tags: - caeel-mitophagy