Disease relevance of LAMP1

• We conclude that neisseria infection results in multiple changes to the lysosomes of infected epithelial cells and that these changes are likely an indirect result of IgA1 protease-mediated cleavage of LAMP1 [1].
• We have localized the polylactosaminoglycans to specific sites on lamp-1 and lamp-2 purified from human chronic myelogenous leukemia cells [2].
• In order to investigate the unique expression of lamp-2, and the gene evolution of lamp-1 and lamp-2, we isolated genomic phage clones encoding these glycoproteins [3].
• Using human leukemia and lymphoma cell lines, we observed a close correlation between CD107a surface expression and target cell lysis, indicating that NK cell cytotoxicity can be assessed by this method [4].
• Indirect immunofluorescence staining revealed accumulation of Lamp molecules at the edges of A2058 human metastasizing melanoma cells suggesting that these glycoproteins could participate in cell adhesion [5].

High impact information on LAMP1

• We isolated pure, viable populations of tumor-cytolytic T cells directly from patient blood samples using flow cytometric quantification of the surface mobilization of CD107a-an integral membrane protein in cytolytic granules-as a marker for degranulation after tumor stimulation [6].
• We combined CD107a mobilization with peptide-major histocompatibility complex (P-MHC) tetramer staining to directly correlate antigen specificity and cytolytic ability on a single-cell level [6].
• In addition to their high endocytic capacity, DCs from GM-CSF + IL-4-dependent cultures are characterized by the presence of a large intracellular compartment that contains high levels of class II molecules, cathepsin D, and lysosomal-associated membrane protein-1, and is rapidly accessible to endocytic markers [7].
• By contrast, MARCKS and PKC alpha remained associated with the phagosome membrane until after acquisition of the lysosomal marker Lamp-1 [8].
• By contrast, depletion of RabGAP-5 results in increased endosome size, more endosome-associated EEA1, and disrupts the trafficking of EGF and LAMP1 [9].

Chemical compound and disease context of LAMP1

• Infection of human epithelial cells by Neisseria meningitidis (MC) and Neisseria gonorrhoeae (GC) increases the rate of degradation of LAMP1, a major integral membrane glycoprotein of late endosomes and lysosomes [10].

Biological context of LAMP1

• Lysosome-associated membrane proteins h-LAMP1 (CD107a) and h-LAMP2 (CD107b) are activation-dependent cell surface glycoproteins in human peripheral blood mononuclear cells which mediate cell adhesion to vascular endothelium [11].
• In contrast, a majority of 'low-fusogenic' phagosomes containing wild-type L. donovani promastigotes do not acquire rab7, wheres they acquire LAMP1 with slower kinetics [12].
• This amino acid sequence suggests that lamp-1 contains a hinge-like structure and could form disulfide bridges that are observed in the immunoglobulin superfamily [13].
• By using the method of in situ hybridization, we have localized the gene for h-lamp-1 to chromosome 13q34 and its related gene to chromosome 12p133 [14].
• Comparison of the exon organization of human lamp-2 and lamp-1 genes, or chicken lamp-1 gene, reveals that these two proteins utilize the same exon phase in corresponding introns [3].

Anatomical context of LAMP1

• By electron and immunofluorescent microscopy analyses, we showed that these structures are acid autolysosomes, containing cellular debris, and labeled by LC3, Rab7, and LAMP1, markers of autophagosomes, late endosomes, and lysosomes, respectively [15].
• Using specific antibodies to ABCA2 and various organelle marker proteins, ABCA2 was found to colocalize with the lysosomal/endosomal marker LAMP1, forming discrete, punctate intracellular vesicles [16].
• LAMP1-positive vacuoles were depleted of PtdIns(3)P in the hVps34-knockdown cells, as judged by their inability to bind the PtdIns(3)P probe GFP-2xFYVE [17].
• We also reported that the IgA1 protease plays a major role in the ability of the pathogenic neisseriae to survive within epithelial cells and hypothesized that this is due to alteration of lysosomes as a result of protease-mediated LAMP1 degradation [1].
• Whereas both live and heat-killed bacteria reside transiently in early endosomes, only live bacteria escape from late endosomes to colocalize in vesicles positive for lysosomal membrane marker LAMP1, endoplasmic reticulum (ER) membrane marker calnexin, and autophagosome marker monodansylcadavarine (MDC) [18].

Associations of LAMP1 with chemical compounds

• Aspirin inhibits surface glycoprotein IIb/IIIa, P-selectin, CD63, and CD107a receptor expression on human platelets [19].
• HL-60 cells were induced to differentiate into granulocytic cells by dimethyl sulfoxide, and structures of Asn-linked oligosaccharides attached to lysosomal membrane glycoproteins (lamp-1 and lamp-2) were elucidated before and after differentiation [20].
• The deduced amino acid sequences indicate that h-lamp-1 and h-lamp-2 consist of 416 and 408 amino acid residues, respectively, and suggest that 27 and 28 NH2-terminal residues are cleavable signal peptides [21].
• These N-glycosylation sites are clustered into two domains separated by a hinge-like structure enriched with proline and serine in h-lamp-1 or proline and threonine in h-lamp-2 [21].
• Toxoplasma-containing vacuoles remained segregated from all levels of the endocytic pathway, as shown by the absence of delivery of transferrin receptors, mannose phosphate receptors, and the lysosomal-associated protein LAMP1 to the vacuole [22].

Physical interactions of LAMP1

• Specifically, HT and TRP-1 may function together via Lamp-1 by stabilizing the enzyme-protein complex within the melanosome and prevent the premature death of melanocytes due to tyrosinase-mediated cytotoxicity [23].
• The bacteria bound readily to Lamp-1 while there was almost no binding to Lamp-2 [24].
• CD63 and Lamp1 interact with amelogenin in vitro [25].
• LAMP-1 at the cell surface has been shown to interact with E-selectin and galectin and is proposed to function in cell-cell interactions [26].

Co-localisations of LAMP1

• HCRP1 cofractionates with Tsg101 and hVps28 by size exclusion chromatography and colocalizes with hVps28 on LAMP1-positive endosomes [27].
• Sucrose gradient ultracentrifugation fractionation of resting platelet sonicates showed that LAMP-2 colocalized with LAMP-1 and with lysosomal enzymes, and not with thrombospondin or serotonin, which are markers of the two other platelet granule compartments, alpha-granules and dense granules [28].

Regulatory relationships of LAMP1

• Cotransfection of genes encoding human tyrosinase and tyrosinase-related protein-1 prevents melanocyte death and enhances melanin pigmentation and gene expression of Lamp-1 [23].
• The enhanced stimulatory capacity of APC expressing LAMP-1-targeted Ags has important implications for vaccine design [29].
• Forskolin blocks the apical expression of dipeptidyl peptidase IV in Caco-2 cells and induces its retention in lamp-1-containing vesicles [30].
• Neisseria gonorrhoeae porin P1.B induces endosome exocytosis and a redistribution of Lamp1 to the plasma membrane [31].

Other interactions of LAMP1

• PRCP antigen does not colocalize with LAMP1 on nonpermeabilized HUVECs, but it partially colocalizes in permeabilized cells [32].
• Kinetic analysis revealed that the majority of the increase in both lamp1 and lamp2 occurred within the first 2 hr of incubation and that a subset of PBMCs maintained expression for at least 96 hr [11].
• In contrast, after ingestion, dead bacteria colocalized with late endosome marker Rab7, and lysosome markers LAMP1 and cathepsin D, but not with calnexin or MDC [18].
• We conclude that HT, TRP-1, and Lamp-1 gene products may function together, being expressed as a multiprotein complex within the melanosomal compartment [23].
• The virus-containing vacuoles were also labeled with antibodies against LAMP-1, CD81, and CD82, which were also incorporated into the viral envelope [33].

Analytical, diagnostic and therapeutic context of LAMP1

• This was accompanied by a reduced expression of the lysosome-associated proteins 1 and 2 (LAMP1 and LAMP2) as determined by both microscopy and Western blot analysis [34].
• Examination of the ultrastructure of lamp-1 by electron microscopy showed that the hinge-like structure actually functions as a hinge [13].
• I-cells analyzed by immunofluorescence microscopy with monoclonal antibodies against hLAMP-1 and hLAMP-2 showed intense staining of the inclusion bodies covering most of the cytoplasm of the cells [35].
• Immunoelectron microscopy confirmed this localization and showed that the hLAMP-positive vesicles commonly contained membrane structures or electron-dense homogeneous material characteristic of secondary lysosomes [35].
• Circular dichroism and nuclear magnetic resonance spectroscopy was used for the structural characterization of a synthetic peptide corresponding to residues 167 to 190 of lamp-1 [36].

References