Disease relevance of Lamp1

• In marked contrast, in PU.1(Pos) mAM(PU.1+) and MH-S cells, adenovirus failed to escape from endosomes, colocalized exclusively with endosome/lysosome markers (Rab5, Rab7, and Lamp1), and rarely expressed the reporter [1].
• Confocal microscopy confirmed that another ER protein, calnexin, colocalizes with Lamp1 on membranes of giant lysosomes from fibroblasts of Chediak-Higashi syndrome patient [2].
• Extracellular lysosome-associated membrane protein-1 (LAMP-1) mediates autoimmune disease progression in the NOD model of type 1 diabetes [3].
• Treatment (from 5 to 25 weeks of age) with a novel blocking monoclonal antibody, mAb I-10, directed against the plasma membrane (pm) form of LAMP-1, protected against development of autoimmune diabetes in the NOD mouse [3].
• Tyrosinase, TRP-2, and LAMP-1 from hybrids migrated more slowly on gels compared to the same proteins from parental melanoma cells, consistent with increased glycosylation [4].

Psychiatry related information on Lamp1

• These results demonstrate that fusing Id to LAMP1 enhances CD8(+) and CD4(+) Id-specific responses for NHLs and may be useful therapeutically [5].

High impact information on Lamp1

• Lysosomal exocytosis and membrane resealing are inhibited by the recombinant Syt VII C(2)A domain or anti-Syt VII C(2)A antibodies, or by antibodies against the cytosolic domain of Lamp-1, which specifically aggregate lysosomes [6].
• 5. Immunoelectron microscopy of infected macrophages and immunoblotting of isolated phagosomes showed that Mycobacterium vacuoles acquire the lysosomal membrane protein LAMP-1, but not the vesicular proton-adenosine triphosphatase (ATPase) responsible for phagosomal acidification [7].
• Flow organellometry and Western blot analysis showed that MTB phagosomes acquired lysosome-associated membrane protein-1 (LAMP-1), MHC-II, and H2-DM [8].
• By 18 h, 70% contained lysosomal-associated membrane protein 1 (LAMP-1) and 40% contained cathepsin D; 50% of the vacuoles could be labeled by endocytosis, and the pH of this population of vacuoles averaged 5 [9].
• After phagocytosis, Nramp1 is acquired by the phagosomal membrane with time kinetics similar to Lamp1, but clearly distinct from those of the early endosomal marker Rab5 [10].

Chemical compound and disease context of Lamp1

• Class II MHC molecules were present in a tubulo-vesicular lysosome compartment, which appeared to fuse with phagosomes, as well as in the resulting phagolysosomes containing internalized Listeria; these compartments were all positive for Lamp 1 and cathepsin D and lacked 46-kD mannose-6-phosphate receptors [11].
• The expression levels of lysosomal membrane glycoprotein 1 and gamma-glutamyltranspeptidase on the cell surface were decreased at 12 h after forskolin treatment, indicating that the bisecting GlcNAc structure may act as a negative sorting signal for the cell surface glycoproteins and may alter the characteristics of hepatoma cells [12].
• In contrast, more than 70% of phagosomes that contained Escherichia coli, polystyrene beads, or exponential phase (E) L. pneumophila matured to phagolysosomes, as judged by co-localization with LAMP-1, cathepsin D and fluorescent endosomal probes [13].

Biological context of Lamp1

• Ionophore-stimulated exocytosis triggered exposure of the luminal domains of both Lamp1 and Syt VII at overlapping sites on the neuronal surface, indicating that the Syt VII-containing lysosomal compartments fuse with the plasma membrane in response to [Ca2+]i elevation [14].
• Because ablation of both the lamp-1 and lamp-2 genes yields an embryonic-lethal phenotype, we were unable to study macrophages from double knockouts [15].
• P2B/LAMP-1 possesses 20 asparagine-linked glycosylation sites separated into equal halves by a central, putative hinge region and is anchored by a carboxy, membrane-spanning, domain [16].
• Surprisingly, LAMP-1 and -2 deficiencies did not affect long-lived protein degradation rates, including proteolysis due to chaperone-mediated autophagy [17].
• Taken together these findings indicate partially overlapping functions for LAMP-1 and -2 in lysosome biogenesis, autophagy, and cholesterol homeostasis [17].

Anatomical context of Lamp1

• The targeting of Lamp1 to lysosomes is dependent on the spacing of its cytoplasmic tail tyrosine sorting motif relative to the membrane [18].
• Lamp1 is a type I transmembrane glycoprotein that is localized primarily in lysosomes and late endosomes [18].
• Distribution and dynamics of Lamp1-containing endocytic organelles in fibroblasts deficient in BLOC-3 [19].
• Upon density gradient centrifugation of organelles of melan-a cells, Oa1 protein colocalized with the late endosomal/lysosomal marker Lamp1, but only partial overlap was observed with melanosomal proteins in the high density region of the gradient [20].
• Lysosome-associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2) are delivered to phagosomes during the maturation process [15].

Associations of Lamp1 with chemical compounds

• By using 3H-glucosamine as a marker of N-glycosylation, its incorporation into tyrosinase and LAMP-1 was found to be elevated in hybrids, suppressed by N-glycosylation inhibitors, and stimulated by MSH to a greater degree in hybrids compared to parental cells [4].
• In these type I and type II granules, MHC class II molecules, mannose-6-phosphate receptors and lysosomal membrane proteins (lamp1 and lamp2) localize to small intralumenal vesicles [21].
• The increased level and glycosylation of both LAMP-1 and LAMP-2 was observed also in cells treated with a synthetic chalcone carboxylic acid analog of RA and by combination of either retinoid with dibutyryl cyclic AMP [22].
• There was no increase in large polylactosaminoglycans of lamp-1 and lamp-2 after retinoic acid treatment, but an increase in the size of small polylactosaminoglycans (included on Bio-Gel P-6) and tri- and tetra-antennary complex oligosaccharides [23].
• In melanocytes treated with U18666A, tyrosinase accumulates in a compartment that contains both lysosome-associated membrane protein-1 (Lamp 1) and MPR, and stains with filipin, consistent with cholesterol-laden late endosomes/lysosomes [24].

Co-localisations of Lamp1

• With confocal microscopy, we found that the typical rodlike shape of the Weibel--Palade body is missing in vWf -/- endothelial cells and that part of the P-selectin content in the vWf -/- cells colocalized with LAMP-1, a lysosomal marker [25].

Other interactions of Lamp1

• LAMP-1 and LAMP-2 are structurally related [26].
• In contrast, colocalization of Oa1 and Oa1-green fluorescent protein fusion product with Lamp1 was extensive throughout the cell [20].
• In LAMP-1-deficient brain, a mild regional astrogliosis and altered immunoreactivity against cathepsin-D was observed [26].
• These results demonstrate an unexpected role for pm-LAMP-1 in autoimmune disease progression, and suggest that further investigation should be performed to understand how this molecule modulates IFN-gamma-driven responses [3].
• We previously have purified and characterized a major lysosomal membrane glycoprotein termed LGP85 (LIMP II) in rat liver lysosomes [27].

Analytical, diagnostic and therapeutic context of Lamp1

• Limited protein sequence analyses of the amino terminal and an internal peptide indicate considerable homology with the LAMP-1 protein [28].
• While we detect only a single message with a mouse LAMP-1 cDNA probe via Northern blotting, Southern analyses indicate the existence of at least two homologous LAMP-1 genes [28].
• In addition, immunoelectron microscopy of normal rat kidney cells showed that lgp120 and vesicular stomatitis virus G-protein were present in the same Golgi cisternae demonstrating that lysosomal and plasma membrane proteins were not sorted either before or during transport through the Golgi apparatus [29].
• LAMP-1 and LAMP-2 were distinguished as different molecules by two-dimensional gel analysis, 125I-tryptic peptide mapping, and sequential immunoprecipitations of 125I-labeled cell extracts [30].
• Indeed, the binding of 125I-labeled L-phytohemagglutinin (L-PHA) to glycoproteins with Mr or 90,000-130,000 increased after differentiation and about 24 times more 125I-labeled L-PHA bound to LAMP-1 isolated by immunoprecipitation from extracts of RA-treated F-9 cells than to LAMP-1 from undifferentiated cells [22].

References