Disease relevance of Lamp1

• The intracellular distributions of the cation-independent mannose 6-phosphate receptor (MPR) and a 120-kD lysosomal membrane glycoprotein (lgp120) were studied in rat hepatoma cells [1].
• Isolation of the gene encoding lamp-1, a lysosomal membrane protein, by differential screening in an animal model of status epilepticus [2].

High impact information on Lamp1

• Here, the lysosomal membrane glycoprotein LGP96 was identified as a receptor for the selective import and degradation of proteins within lysosomes [3].
• Cytoplasmic determinants involved in direct lysosomal sorting, endocytosis, and basolateral targeting of rat lgp120 (lamp-I) in MDCK cells [4].
• Rat lysosomal glycoprotein 120 (lgp120; lamp-I) is a transmembrane protein that is directly delivered from the trans-Golgi network (TGN) to the endosomal/lysosomal system without prior appearance on the cell surface [4].
• AVd were positive for cathepsin D and lgp120 [5].
• However, unlike nascent vacuoles vet comparable to degradative vacuoles, these vacuoles were acidic and contained the lysosomal membrane protein, lgp120, at the outer limiting membrane [6].

Biological context of Lamp1

• The autophagy induced in mitotic cells was inhibited by amino acids, and the resulting autophagosomes contained proteins LC3 and Lamp1, known to be associated with autophagosomes in interphase cells [7].
• The deduced amino acid sequence demonstrates that lgp120 contains a putative signal peptide, 18 sites for N-linked glycosylation, a single membrane-spanning segment, and a short (11 amino acid) cytosolic tail [8].
• To study the kinetics of appearance of endocytic tracers in MPR-and/or lgp120-containing pools in greater detail, cells were allowed to endocytose horse-radish peroxidase (HRP) for 5-90 min [1].
• Depletion of Lamp-1 and Lamp-2 had no measurable effect on endosomal/lysosomal pH, osmotic stability, or density, and cell viability was maintained [9].
• We used the oligonucleotide probe corresponding to the internal amino acid sequence of a lysosomal membrane glycoprotein with a molecular weight of 85 K (LGP85) and isolated and characterized cDNA clones containing the entire coding region [10].

Anatomical context of Lamp1

• To determine the basis for its selective transport to and stability in lysosomes, we have investigated the structure of lgp120 [8].
• Intracellularly, MPR mainly occurred in the trans-Golgi reticulum (TGR) and endosomes. lgp120, on the other hand, was confined to endosomes and lysosomes [1].
• In contrast, lgp120 was not detectable at the plasma membrane [1].
• The lysosomal membrane marker, lgp120, was associated with a separate population of swollen vacuoles that did not contain detectable Man6P receptors [11].
• Indirect immunofluorescence labeling of normal rat kidney (NRK) cells with antibodies recognizing a lysosomal glycoprotein (LGP 120; Lewis, V., S.A. Green, M. Marsh, P. Vihko, A. Helenius, and I. Mellman, 1985, J. Cell Biol., 100:1839-1847) reveals that lysosomes accumulate in the region around the microtubule-organizing center (MTOC) [12].

Associations of Lamp1 with chemical compounds

• Prelysosomelike and lysosomelike structures in ultrathin cryosections of M cells reacted with polyclonal antibody to a membrane glycoprotein (lgp120) enriched in prelysosomes and lysosomes [13].
• In contrast, antibodies to the receptors for asialoglycoproteins and mannose-6-phosphate or to the lysosomal membrane protein, lgp120, distributed to endosomes or lysosomes, respectively, without accumulating in the subapical area [14].
• Asparagine-linked oligosaccharides protect Lamp-1 and Lamp-2 from intracellular proteolysis [9].
• One correlated to lgp120-positive (pre)lysosomes and was still observed after treatment with brefeldin A (BFA), while the other appeared to be partially associated with Golgi membranes and was BFA-sensitive [15].
• PT cells accumulated 109Cd7MT-1 in membrane vesicles associated with the late endo/lysosomal marker LAMP1 but less with the early endosomal marker Rab5a, which was abolished by chloroquine or LY-294002 [16].

Other interactions of Lamp1

• Comparison of LGP 96 and recently cloned lysosomal membrane glycoprotein sequences reveals strong similarity in the putative transmembrane domain and cytoplasmic tail [17].
• LGP85 appears to be an unique lysosomal membrane glycoprotein that does not require tyrosine residues for targeting to lysosomes [10].
• Prolonged exposure to these agents caused redistribution of many labeled vesicles to the perinuclear region, colocalized with markers of both early (EEA1 and transferrin receptor) and late (LAMP1) endosomes [18].
• In the lgp120-positive AVs (lysosomes), the ratio was only 43% of the cytosolic value, consistent with substantial CAIII degradation [19].
• Consistent with this, annexin VI was predominantly seen on structures that contained the lysosomal protein lgp120, although not on dense core lysosomes by electron microscopy [15].

Analytical, diagnostic and therapeutic context of Lamp1

• The reduction in detectability of MPR and lgp120 antigenicity on Western blots, due to treatment of cell homogenates with 3'3-diaminobenzidine, was followed in time [1].
• Thapsigargin also induced the formation of large lgp120-containing vesicles, detected by both confocal and transmission electron microscopy [20].
• Northern blot analysis also demonstrated the presence of lamp-1 transcripts in non-neural tissues [2].
• In parallel with the changes in cathepsins, we found that the amounts of LGP120, LGP110, and LGP85, three integral lysosomal membrane proteins, declined significantly after hepatectomy, suggesting that the lysosomal levels are also diminished in regenerating liver [21].
• Wild-type cathepsin E expressed in human embryonic kidney 293T cells was mainly found in the LAMP-1-positive endosomal organelles, as determined by immunofluorescence microscopy [22].

References