ALLO-1 (allophagy-1, R102.5) is a nematode-specific selective autophagy receptor (cargo adaptor) that drives allophagy. Allophagy is the autophagic removal of sperm-derived (paternal) mitochondria and membranous organelles from the early C. elegans embryo, and it underlies maternal inheritance of mitochondrial DNA. ALLO-1 is expressed in the oocyte germline. Within about a minute of fertilization it gathers on ubiquitin-modified paternal organelles. Through an N-terminal LC3-interacting region (LIR) motif it binds the Atg8/LC3 homolog LGG-1. It is also needed to recruit the ULK complex (UNC-51 and EPG-7/FIP200) around the cargo, so that autophagosomes form locally. Two splice isoforms differ in their C-termini and prefer different cargo: ALLO-1a mainly targets membranous organelles, and its C-terminal coiled-coil region binds K48- and K63-linked polyubiquitin. ALLO-1b mainly targets paternal mitochondria. The TBK1/IKKepsilon-family kinase IKKE-1 binds ALLO-1 and phosphorylates it, which is needed for ALLO-1 to accumulate on the cargo. ALLO-1 and IKKE-1 thus form a positive feedback loop that starts autophagosome formation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000045 autophagosome assembly | IMP PMID:29255173 The autophagy receptor ALLO-1 and the IKKE-1 kinase control ... | ACCEPT | Summary: allo-1 mutants fail to form autophagosomes around paternal organelles after fertilization. ALLO-1 is also needed to recruit LGG-1 and the ULK complex (UNC-51, EPG-7) around the cargo. Reason: ALLO-1 does part of the work of autophagosome assembly at the cargo by recruiting the ULK complex and LGG-1. This is direct participation, as for other cargo receptors. The cached 2018 paper is abstract-only, but the 2024 full-text follow-up confirms the recruitment role. Supporting Evidence: PMID:29255173 ALLO-1 is essential for autophagosome formation around paternal organelles PMID:38368448 We observed that localization of EPG-7-GFP and UNC-51-GFP around paternal organelles was severely impaired in the allo-1 mutant (Supplementary Fig. 5a, b), indicating that ALLO-1 is required for recruitment of the ULK complex around cargo. |
| GO:0005515 protein binding | IPI PMID:14704431 A map of the interactome network of the metazoan C. elegans. | REMOVE | Summary: Large-scale yeast two-hybrid interaction with TRPP-3 (P34605) from the worm interactome map. Reason: Generic protein binding from a high-throughput Y2H screen. It is uninformative and has no known functional link to allophagy. Removing it does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:29255173 The autophagy receptor ALLO-1 and the IKKE-1 kinase control ... | REMOVE | Summary: Interaction with IKKE-1 (P32742). IKKE-1 binds ALLO-1 directly through the ALLO-1 N-terminus and phosphorylates it on Thr-74. Reason: The interaction is real and important, but ALLO-1 is the substrate of the kinase. Generic protein binding adds no functional information about ALLO-1's own activity. The regulatory relationship is better recorded as phosphorylation of ALLO-1 by IKKE-1 than as an ALLO-1 MF. Supporting Evidence: PMID:29255173 IKKE-1 interacts with ALLO-1, and the IKKE-1-dependent phosphorylation of ALLO-1 is important for paternal organelle clearance. |
| GO:0005515 protein binding | IPI PMID:29255173 The autophagy receptor ALLO-1 and the IKKE-1 kinase control ... | MODIFY | Summary: Interaction with LGG-1 (Q09490) through the ALLO-1 LIR motif. Reason: The direct binding of ALLO-1 to LGG-1 through its LIR, together with its recruitment to ubiquitinated cargo, is the defining activity of an autophagy cargo adaptor. This interaction is better captured by the cargo adaptor MF term. ALLO-1 targets both paternal mitochondria and membranous organelles, so the general cargo adaptor term fits better than the mitochondrion-specific adaptor term (GO:0140580). Proposed replacements: autophagy cargo adaptor activity Supporting Evidence: PMID:29255173 directly binds to the worm LC3 homologue LGG-1 through its LC3-interacting region (LIR) motif |
| GO:0005737 cytoplasm | IDA PMID:29255173 The autophagy receptor ALLO-1 and the IKKE-1 kinase control ... | ACCEPT | Summary: ALLO-1 forms cytoplasmic puncta in oocytes and gathers around paternal organelles in the zygote cytoplasm. Reason: The location is correct, though general. Its active location is on the surface of paternal organelles in the cytoplasm. Supporting Evidence: PMID:29255173 After fertilization, ALLO-1 accumulates on the paternal organelles before autophagosome formation |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Mapped from the UniProt subcellular location (cytoplasm). Reason: This is consistent with the IDA annotation. Supporting Evidence: PMID:29255173 After fertilization, ALLO-1 accumulates on the paternal organelles before autophagosome formation |
| GO:0005783 endoplasmic reticulum | HDA PMID:21611156 Determining the sub-cellular localization of proteins within... | KEEP AS NON CORE | Summary: Endoplasmic reticulum, from a high-throughput GFP-fusion survey of protein localisation in body-wall muscle. Reason: This comes from a large-scale reporter survey in muscle, a tissue where ALLO-1 has no known function. Its documented expression and function are in the oocyte germline and embryo. The experimental observation is kept as non-core. Supporting Evidence: PMID:21611156 Our goal in this study is to generate a comprehensive "localizome" for C. elegans body wall muscle by GFP-tagging proteins expressed in muscle and determining their location within the cell. |
| GO:0010506 regulation of autophagy | IMP PMID:29255173 The autophagy receptor ALLO-1 and the IKKE-1 kinase control ... | KEEP AS NON CORE | Summary: Regulation of autophagy, IMP. UniProt notes a role for ALLO-1 in regulating autophagy in germ cells. Reason: The cached paper is abstract-only, so this defers to the curator. ALLO-1's main role is as a direct cargo adaptor in allophagy rather than as a general regulator of autophagy, so this is non-core. Supporting Evidence: PMID:29255173 Here, we identified an autophagy receptor for allophagy, ALLO-1. |
| GO:0030017 sarcomere | HDA PMID:21611156 Determining the sub-cellular localization of proteins within... | KEEP AS NON CORE | Summary: Sarcomere, from the high-throughput body-wall muscle localisation survey. Reason: This is a large-scale GFP reporter result in a tissue where ALLO-1 has no known function. It is kept as non-core. Supporting Evidence: PMID:21611156 Our goal in this study is to generate a comprehensive "localizome" for C. elegans body wall muscle by GFP-tagging proteins expressed in muscle and determining their location within the cell. |
| GO:0042803 protein homodimerization activity | IDA PMID:29255173 The autophagy receptor ALLO-1 and the IKKE-1 kinase control ... | KEEP AS NON CORE | Summary: ALLO-1 self-associates. The ALLO-1a C-terminal region forms a parallel coiled-coil in the crystal structure. Reason: Self-association is supported by the original IDA and by the later structure, but it is a structural property and not the protein's core function. The cached 2018 paper is abstract-only. Supporting Evidence: PMID:41234204 X-ray crystallography analysis reveals that the C-terminal region of ALLO-1a forms a parallel coiled-coil structure. |
| GO:0055120 striated muscle dense body | HDA PMID:21611156 Determining the sub-cellular localization of proteins within... | KEEP AS NON CORE | Summary: Striated muscle dense body, from the high-throughput body-wall muscle localisation survey. Reason: This is a large-scale GFP reporter result in a tissue where ALLO-1 has no known function. It is kept as non-core. Supporting Evidence: PMID:21611156 Our goal in this study is to generate a comprehensive "localizome" for C. elegans body wall muscle by GFP-tagging proteins expressed in muscle and determining their location within the cell. |
| GO:0000423 mitophagy | IMP PMID:38368448 ALLO-1- and IKKE-1-dependent positive feedback mechanism pro... | NEW | Summary: Paternal mitochondria persist in allo-1 mutant embryos. ALLO-1b, the canonical UniProt isoform, gathers on paternal mitochondria within 30 s of sperm-oocyte contact and efficiently rescues their degradation. Reason: ALLO-1 does part of the work of mitophagy. It binds the cargo and LGG-1, and recruits the ULK complex around the mitochondria. Comparator check (QuickGO), for receptors in the same role: human FUNDC1 and BNIP3 are annotated to mitophagy (GO:0000423), and OPTN to its child, type 2 mitophagy. Paternal mitochondrion clearance is a selective autophagy of mitochondria, and no more specific GO term for allophagy exists. ALLO-1 also targets membranous organelles, which this term does not cover. Supporting Evidence: PMID:38368448 In contrast to ALLO-1a, the expression of GFP-ALLO-1b efficiently rescued the defective degradation of paternal mitochondria (Fig. 2a, b). PMID:29255173 In Caenorhabditis elegans embryos, paternally provided organelles, including mitochondria, are eliminated by a process of selective autophagy called allophagy |
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Download this section (compressed HTML)Q: Which ubiquitin ligase(s) mark paternal mitochondria versus membranous organelles, and does ALLO-1b bind ubiquitin through a different interface from ALLO-1a?
Q: Should GO have a process term for elimination of paternal organelles or mitochondria after fertilization (allophagy), as a child of mitophagy/selective autophagy?
Q: Does ALLO-1 act outside the zygote, for example in the reported germ cell regulation of autophagy, and through what cargo?
Experiment: In vitro reconstitution with ubiquitinated liposomes or isolated sperm mitochondria, recombinant ALLO-1a/b, LGG-1 and EPG-7, to test whether ALLO-1 alone bridges cargo to LC3 and the ULK scaffold, and how IKKE-1 phosphorylation of Thr-74 changes this.
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