Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20645 (mannose-6-phosphate receptor)
 320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methotrexate (MTX) covalently linked to poly(L-lysine) [poly(Lys)] enters cells by endocytosis, is degraded in lysosomes and, upon liberation of small molecular methotrexate, is cytocidal to Chinese hamster cells in culture. This drug conjugate was used to select mutants resistant to MTX-poly(Lys), which were examined for defects in endocytosis. Two mutants resistant to MYX-poly(Lys) and sensitive to free MTX, MPL 3-4 and MPL 2-5, internalized the conjugate in normal fashion, but had a decreased ability to degrade it to small molecular drug. The magnitude of this defect in the two mutants correlated with their level of resistance. In addition, both mutants were cross resistant to diphtheria toxin and modeccin and hypersensitive to ricin. While MPL 3-4 internalized MTX-poly(Lys) and inulin normally, it showed decreased endocytosis via the mannose-6-phosphate receptor and decreased uptake of 125I-alpha-2 macroglobulin. Acidification of subcellular fractions was measured using the partitioning of acridine orange. In MPL 3-4, the ATP-driven acidification of the endosome-containing cell fractions was slightly decreased (80% of controls), while acidification of the heavy lysosome-containing fraction was normal. Complementation analysis using hybrids of MPL 3-4 x MPL 2-5 indicated that the mutations occurred at the same gene, but were expressed with different severity. This genotype is identical to that of the End 2 mutants described by Roff et al. (1986). Thus, surprisingly, mutants with identical genotypes were isolated independently by totally different selection procedures.
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PMID:Methotrexate-poly(lysine) as a selective agent for mutants of Chinese hamster ovary cells defective in endocytosis. 337 97

Chlamydiae are obligate intracellular pathogens that reside within a membrane-bound vacuole throughout their developmental cycle. In this study, the intraphagosomal pH of Chlamydia pneumoniae (Cpn) was qualitatively assessed, and the intracellular fate of the pathogen-containing vacuole and its interaction with endocytic organelles in human epithelial cells were analysed using conventional immunofluorescence and confocal microscopy. The pH-sensitive probes acridine orange (AO), LysoTracker (LyT) and DAMP did not accumulate in the bacterial inclusion. In addition, exposure of cells to bafilomycin A1(BafA1), a potent acidification inhibitor, did not inhibit or delay chlamydial growth. The chlamydial compartment was not accessible to the fluid-phase tracer Texas Red (TR)-dextran and did not exhibit any level of staining for the late endosomal marker cation-independent mannose-6-phosphate receptor (Ci-M6PR) or for the lysosomal-associated membrane proteins (LAMP-1 and -2) and CD63. In addition, transferrin receptor (TfR)-enriched vesicles were observed close to Cpn vacuoles, potentially indicating a specific translocation of these organelles through the cytoplasm to the vicinity of the vacuole. We conclude that Cpn, like other chlamydial spp., circumvents the host endocytic pathway and inhabits a non-acidic vacuole, which is dissociated from late endosomes and lysosomes, but selectively accumulates early endosomes.
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PMID:Characterization and intracellular trafficking pattern of vacuoles containing Chlamydia pneumoniae in human epithelial cells. 1120 56