LMP-1 is one of two Caenorhabditis elegans LAMP-family (lysosome-associated membrane glycoprotein) proteins. It is a 237-residue single-pass type I membrane glycoprotein with a heavily N-glycosylated luminal domain, a single transmembrane helix and a short cytoplasmic tail ending in a GYXX(phi) lysosomal targeting motif. LMP-1 resides mainly in the limiting membrane of lysosomes and late endosomes, and in intestinal cells it also marks gut granules (lysosome-related organelles), nonacidic late lysosomes and phagolysosomes; a minor pool is found at the basolateral plasma membrane. Its delivery to gut granules depends on AP-3. No molecular activity has been demonstrated. lmp-1 deletion mutants are viable but have an altered population of intestinal granules, and raising LMP-1 (with LMP-2) levels protects lysosomal membrane integrity in scav-3 mutants, which fits the protective luminal glycocalyx role proposed for mammalian LAMPs. LMP-1 fusions are widely used as lysosome markers in C. elegans.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005764 lysosome | IEA GO_REF:0000117 | ACCEPT | Summary: Lysosome location from an ARBA rule; correct for LMP-1. Reason: Root organelle term (lysosome), which is informative and not to be refined away. The ARBA rule itself is not evidence, but the organelle claim is independently established by multiple direct observations of LMP-1 on lysosomes in coelomocytes and embryonic intestine. The sub-compartment (lysosomal membrane) is already carried by IDA rows. Supporting Evidence: PMID:22916203 In wild type, LMP-1::GFP largely associated with conventional lysosomes PMID:26783301 Late endosomes/lysosomes, labeled with the lysosome membrane protein LMP-1::GFP |
| GO:0005765 lysosomal membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Lysosomal membrane location inherited from the LAMP family root; correct and core. Reason: The PAINT node PTN000897064 (PTHR11506 root) is seeded by mammalian LAMP-family members (LAMP1, LAMP2, LAMP3, CD68 and others) and by LMP-1 itself (WB:WBGene00003053), which is expected and shows experimental grounding on the target. LMP-1 is a type I membrane LAMP-family protein with a C-terminal GYXX(phi) lysosomal targeting motif and is directly observed on lysosomal membranes. Supporting Evidence: PMID:10862717 LMP-1 appears to be the only membrane protein in C. elegans that carries a GYXX(phi) vertebrate lysosomal targeting sequence at its C terminus PMID:26783301 Late endosomes/lysosomes, labeled with the lysosome membrane protein LMP-1::GFP |
| GO:0005765 lysosomal membrane | IDA PMID:19403699 Normal formation of a subset of intestinal granules in Caeno... | ACCEPT | Summary: LMP-1::mRFP marks the membrane of nonacidic late lysosomes in adult intestine. Reason: Direct imaging of LMP-1::mRFP on the surface of nonacidic intestinal granules interpreted as terminally matured late lysosomes; consistent with all other localization data. Supporting Evidence: PMID:19403699 LMP-1::mRFP was detected in a subset of nonacidic granules in wild-type N2 PMID:19403699 were mainly localized on the membrane of nonacidic but lysosome-associated membrane protein homologue (LMP-1)-positive intestinal granules |
| GO:0005765 lysosomal membrane | IDA PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | ACCEPT | Summary: LMP-1::GFP labels the lysosomal membrane in coelomocytes. Reason: LMP-1::GFP is used and described as a lysosome membrane protein in coelomocytes; core location. Supporting Evidence: PMID:26783301 Late endosomes/lysosomes, labeled with the lysosome membrane protein LMP-1::GFP |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: A minor plasma-membrane pool of LMP-1 is observed directly; non-core. Reason: LAMPs transit the cell surface, and LMP-1 itself is observed at the (basolateral) plasma membrane of intestinal cells and in neurons, so the inherited location holds. It is a minor, trafficking-related pool relative to the lysosomal membrane. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000897064 · PTHR11506 LAMP family root SUPPORTS TRANSFER Cell-surface LAMP pools are documented for the mammalian seeds and are also observed directly for LMP-1. Supporting Evidence: PMID:22916203 In intestinal cells LMP-1::GFP localized to the basolateral plasma membrane PMID:22225878 a subset of LMP-1 localized to other membrane compartments that were LysoTracker negative, including the plasma membrane PMID:27810910 both cell surface and intracellular distribution of LMP-1 and LMP-2 were observed |
| GO:0016020 membrane | IEA GO_REF:0000120 | MODIFY | Summary: Correct but uninformative; refine to lysosomal membrane. Reason: LMP-1 is a single-pass membrane protein (signal peptide plus one TM helix), so membrane is true but general. The specific supported membrane is the lysosomal membrane, already carried by IDA and IBA rows in this review. Proposed replacements: lysosomal membrane Supporting Evidence: file:worm/lmp-1/lmp-1-uniprot.txt Single-pass type I membrane protein PMID:26783301 Late endosomes/lysosomes, labeled with the lysosome membrane protein LMP-1::GFP |
| GO:0031902 late endosome membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Late endosome membrane location inherited from LAMP1/LAMP2 and LMP-1 itself; supported. Reason: LAMPs reside on late endosomes as well as lysosomes, and a fraction of LMP-1 compartments in embryonic intestine carry the late endosome marker RAB-7. LMP-1 itself is among the IBD seeds, marking experimental grounding on the target. Supporting Evidence: PMID:22916203 In wild type, 30% (n = 122 compartments from 6 embryos) of LMP-1::GFP compartments contained the late endosome marker RAB-7 |
| GO:0031902 late endosome membrane | IDA PMID:26783301 Negative regulation of phosphatidylinositol 3-phosphate leve... | ACCEPT | Summary: LMP-1::GFP marks late endosomes/lysosomes in coelomocytes. Reason: Direct imaging in coelomocytes; LMP-1-positive late endosome/lysosome compartments. Consistent with RAB-7 colocalization in PMID:22916203. Supporting Evidence: PMID:26783301 Late endosomes/lysosomes, labeled with the lysosome membrane protein LMP-1::GFP |
| GO:0044841 gut granule membrane | IDA PMID:10862717 Identification and molecular-genetic characterization of a L... | ACCEPT | Summary: Original localization of LMP-1 to the periphery of intestinal granules. Reason: Abstract-only in cache, but the abstract explicitly states LMP-1 localizes at the periphery of large membrane-bound granules restricted in later stages to intestinal cells (gut granules); independently confirmed by later full-text studies. Supporting Evidence: PMID:10862717 predominantly localized at the periphery of a population of large, membrane-bound organelles, called granules, that are seen throughout the early embryo but in later stages are restricted to the cells of the intestine |
| GO:0044841 gut granule membrane | IDA PMID:22225878 Lysosome-related organelles in intestinal cells are a zinc s... | ACCEPT | Summary: LMP-1 on the membrane of zinc-storing gut granules. Reason: LMP-1 is on the membrane of gut granules (lysosome-related organelles) and is asymmetrically restricted to the LysoTracker-positive lobe of bilobed granules under high zinc. Supporting Evidence: PMID:22225878 positive for membrane localization of CDF-2, LMP-1 and PGP-2 PMID:22225878 LMP-1 was present only in one lobe of bilobed gut granules |
| GO:0044841 gut granule membrane | IDA PMID:22916203 C. elegans BLOC-1 functions in trafficking to lysosome-relat... | ACCEPT | Summary: LMP-1 localizes to PGP-2-containing gut granules in an AP-3-dependent manner. Reason: Antibody staining and GFP fusion show LMP-1 on PGP-2-positive gut granules in the basal intestine, lost in AP-3 mutants; specificity of the antibody was confirmed with lmp-1(nr2045). Supporting Evidence: PMID:22916203 In the basal region of the intestine, LMP-1 localized to PGP-2 containing gut granules PMID:22916203 In a mutant lacking AP-3 function, gut granules containing PGP-2 (white arrowhead) lacked LMP-1 |
| GO:0045335 phagocytic vesicle | IDA PMID:20133524 Retromer is required for apoptotic cell clearance by phagocy... | KEEP AS NON CORE | Summary: LMP-1 on phagosomes containing cell corpses; plausible and independently supported, non-core. Reason: The cited paper is abstract-only in the cache and its abstract does not mention LMP-1, so the figure the curator used cannot be inspected. LMP-1 on phagosomes is however independently reported (UNC-108 colocalizes with LMP-1 on phagosomes), and it is the expected consequence of phagosome-lysosome fusion. The phagosome is a destination of lysosomal membrane rather than a distinct site of LMP-1 function, so non-core. Supporting Evidence: PMID:18256195 UNC-108 co-localizes with RAB-5, RAB-7 and LMP-1 to the phagosome |
| GO:0072594 establishment of protein localization to organelle | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Process seeded by vertebrate LAMP1/LAMP2-specific roles; not shown for LMP-1. Reason: The seeds are LAMP1 (perforin delivery to NK-cell lytic granules) and LAMP2 (LAMP2A as the receptor/translocation component of chaperone-mediated autophagy). Both are vertebrate- or cell-type-specific roles; nematodes lack NK cells and the LAMP2A splice form, and no study shows LMP-1 directing any protein to an organelle. The only LMP-1 functional data are a granule-population phenotype and suppression of lysosomal membrane damage on overexpression, neither of which shows LMP-1 performing protein targeting. Placing this process at the family root over-propagates it to the nematode lineage. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000897064 · PTHR11506 LAMP family root SUPPORTS SOURCE BUT NOT TARGET Seeded only by mammalian LAMP1 and LAMP2 (human, mouse, rat). The underlying roles (NK-cell lytic granule cargo delivery; LAMP2A-dependent chaperone-mediated autophagy) are not documented outside vertebrates, and LMP-1 is not among the seeds for this term. Supporting Evidence: PMID:10862717 the absence of LMP-1 leads to an alteration in intestinal granule populations, with apparent loss of one type of granule PMID:27810910 These data suggest that the increased level of LMP-1 and LMP-2 compensates for the loss of SCAV-3 to maintain lysosome membrane integrity. |
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Download this section (compressed HTML)Q: Does LMP-1 have a specific molecular activity comparable to human LAMP1 inhibition of the TMEM175 proton channel, or is its role purely as a luminal glycocalyx component protecting the lysosomal membrane?
Q: Which granule type is lost in lmp-1(nr2045) intestine, and is the defect one of biogenesis or of maintenance of a lysosome-related organelle subpopulation?
Experiment: Test whether LMP-1 (alone and with LMP-2) binds and modulates a C. elegans TMEM175-family lysosomal channel (if one is present), and measure lysosomal pH and proton leak in lmp-1; lmp-2 double mutants.
Experiment: Measure lysosomal membrane permeabilization (galectin puncta) and hydrolase leakage in lmp-1; lmp-2 double mutants under lysosomal stress to test the glycocalyx protection model.
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Download this section (compressed HTML)lmp-1 encodes a protein with similarity to vertebrate lysosome-associated membrane proteins CD68, and appears to be the only protein in C. elegans that has a GYXX (phi) vertebrate lysosomal targeting sequence at its carboxy terminus; LMP-1 is widely expressed in the early embryo, with later expression seen in the intestine, coelomocytes, and neurons; LMP-1 localizes to lysosomes and is recruited to phagosomes upon lysosomal fusion.
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