VPS-34 (LET-512, B0025.1) is the sole class III phosphatidylinositol 3-kinase of C. elegans, the ortholog of yeast Vps34 and human PIK3C3. It is a lipid kinase that phosphorylates phosphatidylinositol at the D-3 position of the inositol ring to make phosphatidylinositol 3-phosphate (PtdIns3P); immunoprecipitated worm VPS-34 has wortmannin-sensitive PtdIns-specific kinase activity. VPS-34 acts in complexes with the Beclin ortholog BEC-1 and the regulatory kinase VPS-15, and probably with EPG-8/ATG14 (autophagy-specific complex I) or UVRAG (endocytic complex II). The PtdIns3P it makes marks early endosomes, phagosomes and autophagosome formation sites. There it recruits FYVE, PX and WD40 (PROPPIN) effectors that drive endosome fusion and maturation, endosome-to-Golgi retrograde transport, maturation of phagosomes containing apoptotic cells (with the class II PI3K PIKI-1), and autophagosome formation. The protein is expressed in all tissues and concentrates at the nuclear envelope and perinuclear region. Loss of vps-34 is lethal, with arrest at the L3/L4 molts. Mutants have cuticle-shedding defects, an expanded outer nuclear membrane, mislocalised apical LRP-1 and no detectable membrane-bound PtdIns3P. Through its role in autophagy, vps-34 is also needed for the long life span of germline-less animals.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000045 autophagosome assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Autophagosome assembly by PAINT inference from the PIK3C3/Vps34 clade. VPS-34 is the only class III PI3K in C. elegans and the catalytic partner of BEC-1, which is required for autophagy in worms. Reason: Making PtdIns3P at the autophagosome formation site is the conserved core role of the class III PI3K complex I, and C. elegans VPS-34 is inside that clade. Worm data show that BEC-1 is needed for LET-512/VPS-34 function in autophagy, and that the PtdIns3P effectors EPG-6 and ATG-18 act in autophagosome formation. The IBA node placement is sound. Supporting Evidence: PMID:16111945 We demonstrate that BEC-1 is necessary for the function of the class III PI3 kinase LET-512/Vps34, an essential protein required for autophagy, membrane trafficking, and endocytosis. |
| GO:0000407 phagophore assembly site | IBA GO_REF:0000033 | ACCEPT | Summary: Phagophore assembly site location, inferred by IBA. The yeast donor is Vps34, which is recruited to the PAS as part of complex I. Reason: This location is consistent with VPS-34's role in autophagosome nucleation. In worms, the PtdIns3P-binding effector EPG-6 works at omegasomes, which depend on autophagic PtdIns3P. The IBA is accepted. No direct localisation of worm VPS-34 to the phagophore assembly site has been reported. Supporting Evidence: PMID:21802374 PtdIns(3)P plays critical roles in the autophagy pathway. |
| GO:0000425 pexophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Pexophagy, inferred by IBA from yeast Vps34 alone. Reason: Vps34-made PtdIns3P is needed for macroautophagy in general, so a role in selective peroxisome autophagy is plausible across the clade. However, pexophagy has not been studied in C. elegans and the inference comes only from yeast. The term is kept as a non-core, generic consequence of the autophagy function. Supporting Evidence: PMID:16111945 We demonstrate that BEC-1 is necessary for the function of the class III PI3 kinase LET-512/Vps34, an essential protein required for autophagy, membrane trafficking, and endocytosis. |
| GO:0001891 phagocytic cup | IEA GO_REF:0000044 | ACCEPT | Summary: Phagocytic cup location, mapped from the UniProt subcellular location, which is based on Kinchen et al. 2008. In that study, VPS-34 colocalised with RAB-5 and DYN-1 at the phagocytic cup and formed a complex with dynamin and Rab5. Reason: The location is supported by worm data on VPS-34 recruitment to nascent phagosomes during engulfment of apoptotic cells. Supporting Evidence: PMID:18425118 Finally, we have also identified a previously undescribed biochemical complex containing Vps34, dynamin and Rab5(GDP), thus providing a mechanism for Rab5 recruitment to the nascent phagosome. |
| GO:0002119 nematode larval development | IMP PMID:11927551 Membrane transport in Caenorhabditis elegans: an essential r... | KEEP AS NON CORE | Summary: let-512/vps-34 mutants arrest at or shortly after the L3/L4 or L4/adult molts. Reason: The phenotype is real, but it is a pleiotropic result of losing PtdIns3P-dependent membrane trafficking, including secretion of the LDL-receptor LRP-1, rather than a dedicated developmental role. Supporting Evidence: PMID:11927551 Homozygotes segregating from heterozygous mothers were able to hatch and initiate development but they arrested development at or shortly after the molts from L3 to L4 or from L4 to adult. |
| GO:0005515 protein binding | IPI PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | REMOVE | Summary: IPI with BEC-1 (Q22592). GST-BEC-1 pulled down in vitro-translated VPS-34, and BEC-1 co-precipitated Flag-VPS-34 from worm lysates. Reason: The BEC-1/VPS-34 interaction is well established, but the generic protein binding term adds no functional information. The interaction is better captured by the class III PI3K complex terms (GO:0034271/GO:0034272), which are already annotated. VPS-34 is the catalytic subunit, so no adaptor-type MF applies to it. Supporting Evidence: PMID:26783301 In pull-down assays, GST-fused BEC-1 pulled down 35S-labeled SORF-1, SORF-2, and VPS-34 (Fig. 7 F). |
| GO:0005640 nuclear outer membrane | IDA PMID:11927551 Membrane transport in Caenorhabditis elegans: an essential r... | ACCEPT | Summary: Antibody staining shows VPS-34 concentrated at the nuclear envelope/perinuclear region. The authors conclude that it acts at the outer nuclear membrane. Reason: This is direct localisation data in the worm, supported by the outer nuclear membrane expansion phenotype. Supporting Evidence: PMID:11927551 Loss-of-function mutations in let-512/vps34 result in an expansion of the perinuclear space, and our data suggest that LET-512/VPS34 is located to and acts directly at the outer nuclear membrane. |
| GO:0005640 nuclear outer membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Mapped from the UniProt subcellular location (nucleus outer membrane), which is based on PMID:11927551. Reason: This duplicates the IDA annotation and is consistent with it. Supporting Evidence: PMID:11927551 Loss-of-function mutations in let-512/vps34 result in an expansion of the perinuclear space, and our data suggest that LET-512/VPS34 is located to and acts directly at the outer nuclear membrane. |
| GO:0005730 nucleolus | IDA PMID:24154628 Base excision repair AP endonucleases and mismatch repair ac... | KEEP AS NON CORE | Summary: After 5-FU treatment, which induces DNA-repair-dependent autophagy, endogenous VPS-34 formed foci in nucleoli of embryos. Reason: The observation is direct, but it is stress-induced and its functional meaning is unclear. Nucleolar localisation is not part of the core lipid kinase role. Supporting Evidence: PMID:24154628 Distinct VPS-34 foci were also observed in the |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm, inferred by IBA from the wider PI3K family. Reason: VPS-34 is a peripheral membrane protein that cycles between the cytosol and membranes. Diffuse and granular cytoplasmic staining was seen in worms. Supporting Evidence: PMID:11927551 Ce VPS34 was strongly concentrated at a perinuclear localization in all blastomeres of the embryo, but some weak granular and diffuse cytoplasmic anti- Ce VPS34 staining was also evident |
| GO:0005737 cytoplasm | IDA PMID:11927551 Membrane transport in Caenorhabditis elegans: an essential r... | ACCEPT | Summary: Antibody staining shows weak granular and diffuse cytoplasmic VPS-34 in addition to the perinuclear signal. Reason: This is direct worm localisation data. Supporting Evidence: PMID:11927551 Ce VPS34 was strongly concentrated at a perinuclear localization in all blastomeres of the embryo, but some weak granular and diffuse cytoplasmic anti- Ce VPS34 staining was also evident |
| 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:11927551 Ce VPS34 was strongly concentrated at a perinuclear localization in all blastomeres of the embryo, but some weak granular and diffuse cytoplasmic anti- Ce VPS34 staining was also evident |
| GO:0005768 endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Endosome, inferred by IBA. In worms, PtdIns3P made by VPS-34 marks early endosomes. Endosomal PtdIns3P puncta are nearly abolished in maternal/zygotic vps-34 null embryos. Reason: Complex II acts on endosomes, and worm data confirm that VPS-34 makes endosomal PtdIns3P. Supporting Evidence: PMID:22272187 consistent with the known function of VPS-34 in the production of PtdIns(3)P on early endosomes |
| GO:0005777 peroxisome | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Peroxisome (is_active_in), inferred by IBA from yeast Vps34 alone. Reason: There is no evidence that the class III PI3K acts at peroxisomes in metazoans, and no worm data. A transient association during yeast pexophagy does not make the peroxisome a characteristic site of activity for C. elegans VPS-34. The documented sites are endosomes, phagosomes, autophagic membranes and the nuclear envelope. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN000005955 Β· PTN000005955 SUPPORTS SOURCE BUT NOT TARGET The class III PI3K node is correct for the kinase and autophagy. The peroxisome location rests only on yeast Vps34 in a pexophagy context, which has no metazoan or worm support. Supporting Evidence: PMID:11927551 Using a GFP::2xFYVE fusion protein that specifically binds PtdIns 3-P, we found that PtdIns 3-P is associated with a multitude of intracellular membranes and vesicles located at peripheral positions. |
| GO:0006897 endocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: Endocytosis, inferred by IBA. Worm VPS-34-made PtdIns3P marks endocytic vesicles, and vps-34 loss causes defects in coelomocyte endocytosis and in apical LRP-1 trafficking. Reason: Endocytic trafficking is one of the two conserved functions of the class III PI3K, through complex II with UVRAG. Worm data support it. Supporting Evidence: PMID:11927551 Using a GFP::2xFYVE fusion protein we found that the phosphatidylinositol 3-phosphate (PtdIns 3-P) product of LET-512/VPS34 is associated with a multitude of intracellular membranes and vesicles located at the periphery, including endocytic vesicles. PMID:19816564 inactivation of mtm-1 rescued the endocytosis defect in vps-34(lf) coelomocytes |
| GO:0006998 nuclear envelope organization | IMP PMID:11927551 Membrane transport in Caenorhabditis elegans: an essential r... | KEEP AS NON CORE | Summary: let-512 mutants show an expanded outer nuclear membrane/perinuclear space in many tissues. Reason: The authors interpret the expansion as retention of secretory material when vesicle budding from the outer nuclear membrane is blocked. That makes it a consequence of a membrane trafficking defect, not a direct role in organising the nuclear envelope. Supporting Evidence: PMID:11927551 Inactivation of LET-512/VPS34 may block vesicle budding, thereby causing a retention of secretory and biosynthetic material resulting in an expansion of the perinuclear space between the inner and the outer nuclear membrane |
| GO:0008340 determination of adult lifespan | IGI PMID:21906946 Autophagy and lipid metabolism coordinately modulate life sp... | KEEP AS NON CORE | Summary: IGI (with WBGene00001609) from Lapierre et al. 2011. Autophagy genes, including vps-34, are needed for the long life span of germline-less animals. Reason: The cached paper is abstract-only, so this defers to the curator. Life span is a downstream organismal outcome of autophagy, not a core function of the kinase. Supporting Evidence: PMID:21906946 Here, we show that germline loss induces autophagy gene expression via the forkhead box A (FOXA) transcription factor PHA-4 and that autophagy is required to extend longevity. |
| GO:0008340 determination of adult lifespan | IGI PMID:21906946 Autophagy and lipid metabolism coordinately modulate life sp... | KEEP AS NON CORE | Summary: IGI (with WBGene00003219) from the same study. vps-34 knockdown suppresses life span extension in a longevity model. Reason: As above, this is a downstream organismal phenotype of autophagy. Supporting Evidence: PMID:21906946 autophagy is induced in animals overexpressing LIPL-4 and autophagy is required for their long life span |
| GO:0008340 determination of adult lifespan | IGI PMID:21906946 Autophagy and lipid metabolism coordinately modulate life sp... | KEEP AS NON CORE | Summary: IGI (with WBGene00006932) from the same study. Reason: As above, this is a downstream organismal phenotype of autophagy. Supporting Evidence: PMID:21906946 autophagy is required to extend longevity |
| GO:0016020 membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Membrane, inferred by IBA from the PI3K family. Reason: VPS-34 is a peripheral membrane protein that acts on membrane PtdIns. The term is general but correct. Supporting Evidence: PMID:11927551 LET-512/VPS34 is located to and acts directly at the outer nuclear membrane |
| GO:0016301 kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: Kinase activity, inferred from the InterPro PI3/4-kinase domain. Reason: This is correct but much less informative than the experimentally shown PtdIns-specific 3-kinase activity. Proposed replacements: 1-phosphatidylinositol-3-kinase activity Supporting Evidence: PMID:11927551 The anti- Ce VPS34 immunoprecipitate displayed a lipid kinase activity towards PtdIns, yielding PtdIns 3-P as a product. |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: 1-phosphatidylinositol-3-kinase activity, inferred by IBA from the class III PI3K clade, including worm VPS-34's own IDA. Reason: This is the core catalytic activity, conserved across the clade and shown biochemically for the worm protein. The target appearing among its own donors reflects its own experimental grounding. Supporting Evidence: PMID:11927551 The anti- Ce VPS34 immunoprecipitate displayed a lipid kinase activity towards PtdIns, yielding PtdIns 3-P as a product. |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | IDA PMID:11927551 Membrane transport in Caenorhabditis elegans: an essential r... | ACCEPT | Summary: Immunoprecipitated worm VPS-34 phosphorylates PtdIns to make PtdIns3P, and the activity is blocked by wortmannin. Reason: This is a direct biochemical assay of the endogenous worm protein. Supporting Evidence: PMID:11927551 The immunoprecipitate was incubated with PtdIns and [Ξ³- 32 P]ATP, and the reaction products were assayed by thin layer chromatography (TLC) and autoradiography. The anti- Ce VPS34 immunoprecipitate displayed a lipid kinase activity towards PtdIns, yielding PtdIns 3-P as a product. |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | IDA PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | ACCEPT | Summary: PI3K activity was measured on BEC-1 immunoprecipitates from worms expressing Flag-VPS-34, and was elevated in sorf-1/sorf-2 mutants. Reason: This is a direct activity assay of the worm BEC-1/VPS-34 complex. Supporting Evidence: PMID:26783301 However, the activities of BEC-1-VPS-34 complexes from sorf-1 and sorf-2 mutants are nearly two times that from N2 animals (Fig. 7 G). |
| GO:0016303 1-phosphatidylinositol-3-kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (ARBA, InterPro, RHEA:12709/EC 2.7.1.137). Reason: This agrees with the experimental data. Supporting Evidence: PMID:11927551 The anti- Ce VPS34 immunoprecipitate displayed a lipid kinase activity towards PtdIns, yielding PtdIns 3-P as a product. |
| GO:0030100 regulation of endocytosis | IMP PMID:11927551 Membrane transport in Caenorhabditis elegans: an essential r... | KEEP AS NON CORE | Summary: In let-512 mutants, apical LRP-1 is gradually lost and endocytic vesicles become tubular, so the authors suggest a role in receptor-mediated endocytosis or secretion of LRP-1. Reason: VPS-34 is better described as a direct participant in endocytic membrane trafficking (GO:0006897, already annotated) than as a regulator of endocytosis. The authors could not tell a secretion defect apart from an endocytic one. The annotation is kept but is not core. Supporting Evidence: PMID:11927551 Thus, let-512/vps34 mutant animals have defects in the secretion and/or in the production of LRP-1. |
| GO:0034271 phosphatidylinositol 3-kinase complex, class III, type I | IBA GO_REF:0000033 | ACCEPT | Summary: Class III PI3K complex I (autophagy-specific, with Atg14), inferred by IBA. In worms, BEC-1 binds VPS-34, and EPG-8, the divergent Atg14 homolog, binds BEC-1. Reason: The worm complex I subunits are present and interact. The catalytic subunit belongs in this complex. Supporting Evidence: PMID:21116129 EPG-8 directly interacts with the C. elegans Beclin 1 homolog, BEC-1. PMID:26783301 In pull-down assays, GST-fused BEC-1 pulled down 35S-labeled SORF-1, SORF-2, and VPS-34 (Fig. 7 F). |
| GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II | IBA GO_REF:0000033 | ACCEPT | Summary: Class III PI3K complex II (endocytic, with UVRAG/Vps38), inferred by IBA. Reason: The catalytic subunit is shared by both complexes. The endocytic and endosome-to-Golgi functions of BEC-1/VPS-34 in worms fit complex II. Supporting Evidence: PMID:26783301 We next examined the requirement for the class III PI3K complex, which is composed of VPS-34, BEC-1, and VPS-15/p150. |
| GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PtdIns3P biosynthetic process, inferred by IBA. Reason: This is the core process carried out by the kinase activity. Supporting Evidence: PMID:11927551 The anti- Ce VPS34 immunoprecipitate displayed a lipid kinase activity towards PtdIns, yielding PtdIns 3-P as a product. |
| GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process | IDA PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | ACCEPT | Summary: The BEC-1/VPS-34 complex from worms has PI3K activity, and vps-34 RNAi abolishes endosomal PtdIns3P-dependent recruitment of effectors. Reason: Direct activity data support this term. Supporting Evidence: PMID:26783301 The endosomal enrichment of GFP::SORF-1/SORF-2 was abolished with vps-34 RNAi (Fig. 7 J). |
| GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process | IMP PMID:22272187 Two PI 3-kinases and one PI 3-phosphatase together establish... | ACCEPT | Summary: Maternal/zygotic vps-34 null embryos lose endosomal PtdIns3P and have reduced phagosomal PtdIns3P. piki-1; vps-34 double mutants have no phagosomal PtdIns3P. Reason: The genetic data agree with the catalytic activity. Supporting Evidence: PMID:22272187 Inactivating both piki-1 and vps-34 completely abolishes the production of phagosomal PtdIns(3)P |
| GO:0042395 ecdysis, collagen and cuticulin-based cuticle | IMP PMID:11927551 Membrane transport in Caenorhabditis elegans: an essential r... | KEEP AS NON CORE | Summary: let-512 mutants fail to shed the old cuticle at the molt, a phenotype like that of lrp-1 mutants. Reason: The molting defect is probably secondary to the failure to traffic LRP-1 to the apical hypodermal surface. It is a pleiotropic outcome of the trafficking defect. Supporting Evidence: PMID:11927551 The severe defects in molting and in the proper shedding of the old cuticle displayed by arrested homozygous let-512(h510) mutant worms resembled the defects caused by mutations in the C.elegans gene lrp-1 |
| GO:0046854 phosphatidylinositol phosphate biosynthetic process | IEA GO_REF:0000002 | ACCEPT | Summary: Phosphatidylinositol phosphate biosynthetic process, an InterPro IEA. Reason: This is a correct parent of PtdIns3P biosynthesis. Supporting Evidence: PMID:11927551 The anti- Ce VPS34 immunoprecipitate displayed a lipid kinase activity towards PtdIns, yielding PtdIns 3-P as a product. |
| GO:0048015 phosphatidylinositol-mediated signaling | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Phosphatidylinositol-mediated signaling, inferred by IBA from a broad PI3K node (PTN000005673) whose donors are class I/II PI3Ks (FB PI3K92E-type, dictyBase). Reason: Class III PI3K makes PtdIns3P as a constitutive membrane identity cue for trafficking and autophagy, not as a second messenger in receptor signaling. The donors behind this deep node are class I enzymes, and the term does not describe VPS-34's role well. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN000005673 Β· PTN000005673 SUPPORTS SOURCE BUT NOT TARGET This deep PI3K node is seeded by class I/II signaling PI3Ks. Second-messenger signaling does not describe the class III trafficking enzyme. Supporting Evidence: PMID:11927551 We propose that LET-512/VPS34 is required for membrane transport from the outer nuclear membrane towards the cell periphery. |
| GO:0050708 regulation of protein secretion | IMP PMID:11927551 Membrane transport in Caenorhabditis elegans: an essential r... | KEEP AS NON CORE | Summary: let-512 mutants fail to put LRP-1 at the apical surface of hyp7. The authors propose a role in secretion of LRP-1. Reason: The phenotype is consistent with a general membrane trafficking defect, and the authors cannot tell secretion apart from production of LRP-1. The annotation is kept as non-core. Supporting Evidence: PMID:11927551 From these experiments we concluded that the function of LET-512/VPS34 is required for the secretion and localization of LRP-1 at the apical surface of the hypodermal syncytium of C.elegans . |
| GO:0051036 regulation of endosome size | IGI PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | KEEP AS NON CORE | Summary: IGI with sorf-1/sorf-2 and rab-7. vps-34 RNAi suppresses the giant early endosomes of rab-7; sorf double mutants. Reason: Endosome size depends on PtdIns3P levels, which VPS-34 sets. Endosome size control is a consequence of PtdIns3P synthesis, not a separate function. Supporting Evidence: PMID:26783301 RNAi of vps-34, bec-1, and Y34B4a.2 suppresses enlargement of early endosomes in hypodermal cells in double mutants of rab-7(ok511) with sorf-1(tm3855) or sorf-2(tm5210). |
| GO:0051036 regulation of endosome size | IGI PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | KEEP AS NON CORE | Summary: The same IGI with a different interactor pair. Reason: As above, endosome size control is a consequence of PtdIns3P synthesis. Supporting Evidence: PMID:26783301 RNAi of vps-34, bec-1, and Y34B4a.2 suppresses enlargement of early endosomes in hypodermal cells in double mutants of rab-7(ok511) with sorf-1(tm3855) or sorf-2(tm5210). |
| GO:0090386 phagosome maturation involved in apoptotic cell clearance | IGI PMID:22272187 Two PI 3-kinases and one PI 3-phosphatase together establish... | ACCEPT | Summary: IGI with piki-1. VPS-34 and the class II PI3K PIKI-1 act in sequence to make the waves of phagosomal PtdIns3P needed to degrade apoptotic cells. Reason: VPS-34 directly makes the PtdIns3P that recruits maturation effectors (SNX-1, LST-4, RAB-5/7) to phagosomes. This is a well-established role in worms. Supporting Evidence: PMID:22272187 PIKI-1 and VPS-34 act in sequence to provide overlapping pools of PtdIns(3)P on phagosomes. PMID:18425118 showed an accumulation of internalized, but undegraded, corpses within abnormal Rab5-negative phagosomes |
| GO:0090386 phagosome maturation involved in apoptotic cell clearance | IMP PMID:22272187 Two PI 3-kinases and one PI 3-phosphatase together establish... | ACCEPT | Summary: IMP. vps-34 mutants have delayed phagosome maturation and reduced phagosomal PtdIns3P. Reason: Direct worm mutant evidence supports this term. Supporting Evidence: PMID:22272187 Interestingly, the phagosome maturation-delay/arrest phenotype observed from C. elegans vps-34 mutants was much milder than that from the ced-1 or dyn-1 single mutants |
| GO:0160108 animal gross anatomical part developmental process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Animal gross anatomical part developmental process, from an ARBA machine-learning IEA. Reason: This is a vague developmental grouping term with no specific supporting evidence. Developmental phenotypes of vps-34 are pleiotropic results of its trafficking role. Supporting Evidence: PMID:11927551 LET-512/VPS34 has essential functions and is ubiquitously expressed in all tissues and developmental stages. |
| GO:1901076 positive regulation of engulfment of apoptotic cell | IGI PMID:19816564 Caenorhabditis elegans myotubularin MTM-1 negatively regulat... | KEEP AS NON CORE | Summary: IGI with piki-1. Fewer cell corpses after mtm-1 RNAi depends on VPS-34 and PIKI-1. Reason: The genetic result is sound. However, the best-supported role of VPS-34 in corpse clearance is phagosome maturation after internalisation. vps-34 mutants accumulate internalised but undegraded corpses. Corpse counts do not separate engulfment from degradation, so the term is kept as non-core. Supporting Evidence: PMID:19816564 We show that the reduction of cell corpses caused by mtm-1 RNAi requires the functions of CED-5, CED-12 and CED-10 and the activities of PI3-kinases VPS-34 and PIKI-1. |
| GO:1901076 positive regulation of engulfment of apoptotic cell | IMP PMID:21183797 The Atg6/Vps30/Beclin 1 ortholog BEC-1 mediates endocytic re... | KEEP AS NON CORE | Summary: IMP from Ruck et al. 2011, a BEC-1 paper that also used vps-34 RNAi. The cached copy is abstract-only. Reason: This defers to the curator, who saw the full text. Mechanistically, VPS-34 acts mainly in phagosome maturation rather than in engulfment. Supporting Evidence: PMID:21183797 We further identify a requirement for BEC-1 in the clearance of apoptotic corpses in the hermaphrodite gonad, suggesting a role for BEC-1 in phagosome maturation |
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Download this section (compressed HTML)Q: What makes VPS-34 concentrate at the nuclear envelope, and does the perinuclear pool belong to complex I, complex II, or a different assembly?
Q: Is a worm UVRAG ortholog (complex II-specific subunit) needed for the endocytic and phagosomal functions of VPS-34, and what is it?
Experiment: Degron or tissue-specific depletion of endogenous VPS-34, combined with GFP-tagged EPG-8 or a UVRAG candidate, to separate the autophagic complex I functions from the endocytic complex II functions in the same tissue.
Experiment: Immuno-EM of endogenously tagged VPS-34 to test whether the perinuclear pool is on the outer nuclear membrane or on adjacent ER/omegasome membranes.
vps-34 encodes an ortholog of the phosphoinositide 3-kinase VPS34 in S. cerevisiae, a protein that regulates multiple steps in endocytosis, and that is required for growth at normal rates during development; in C. elegans, vps-34 is required for vesicular trafficking, including endocytosis, apoptotic cell clearance, and autophagy.
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