Disease relevance of Lamp2

• Differentiation of the murine embryonal carcinoma (EC) cell lines F-9 and PC-13, induced by beta-all transretinoic acid (RA) resulted in an increased level of two lysosomal-associated membrane glycoproteins (LAMP-1 and LAMP-2) [1].
• Morphological, clinical and genetic aspects in a family with a novel LAMP-2 gene mutation (Danon disease) [2].
• Mutations in LAMP-2 gene cause a lysosomal glycogen storage disease, Danon disease, in humans [3].
• Neither Rab7, a marker of late endosomes, nor LAMP-2 lysosomal glycoprotein was found to colocalize with polyomavirus [4].

Psychiatry related information on Lamp2

• OBJECTIVE: Mutations in the highly glycosylated lysosome associated membrane protein-2 (LAMP-2) cause, as recently shown, familial Danon disease with mental retardation, mild myopathy and fatal cardiomyopathy [5].

High impact information on Lamp2

• Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice [6].
• These findings indicate that LAMP-2 is critical for autophagy [6].
• This theory is further substantiated by the finding that human LAMP-2 deficiency causing Danon's disease is associated with the accumulation of autophagic material in striated myocytes [6].
• Histochemistry and immunofluorescence showed that the giant organelles in both beige and CHS fibroblasts were positive for cathepsin D, lysosome-associated membrane protein (LAMP) 1, LAMP 2, and a 120-kD lysosomal glycoprotein, all marker proteins for late endosomes and lysosomes [7].
• Macrophages from LAMP-1- or LAMP-2-deficient mice displayed normal fusion of lysosomes with phagosomes [8].

Biological context of Lamp2

• 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 [8].
• The lysosomal-associated membrane glycoproteins LAMP-1 and LAMP-2 are the major carriers of this glycosylation pattern [9].
• LAMP-1 appears late in spermatogenesis (Acrosome-phase) contrasting with LAMP-2, which is present throughout the complete process [10].
• Melan-b cells showed the same gene expression of LAMP-1, LAMP-2 and LAMP-3 as that of non-UV exposed cells [11].
• Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy [3].

Anatomical context of Lamp2

• Lysosome-associated membrane proteins 1 and 2 (LAMP-1 and LAMP-2) are delivered to phagosomes during the maturation process [8].
• Time-lapse cinematography revealed that late endosomes/lysosomes as well as phagosomes lacking LAMP-1 and LAMP-2 had reduced ability to move toward the microtubule-organizing center, likely precluding their interaction with each other [8].
• Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts [12].
• Lysosomal membranes contain two highly glycosylated proteins, designated LAMP-1 and LAMP-2, as major components [13].
• Our data indicate that in hepatocytes LAMP-2 deficiency either directly or indirectly leads to impaired recycling of 46-kDa mannose 6-phosphate receptors and partial mistargeting of a subset of lysosomal enzymes [14].

Associations of Lamp2 with chemical compounds

• The LAMP-1/2 double-deficient cells and, to a lesser extent, LAMP-2 single-deficient cells showed an accumulation of unesterified cholesterol in endo/lysosomal, rab7, and NPC1 positive compartments as well as reduced amounts of lipid droplets [12].
• 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 [15].
• 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 [1].
• 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 [16].
• The phagosomes containing live M. ptb and M. avium were significantly reduced in their ability to acquire some markers for the endocytic pathway, such as internalized calcein, BSA-gold or the membrane protein Lamp 2 [17].

Co-localisations of Lamp2

• After stimulation, the V-ATPase with the a3 isoform was immunochemically colocalized with lysosome marker lamp2 and was detected in acidic organelles [18].

Other interactions of Lamp2

• LAMP-1 and LAMP-2 are structurally related [13].
• In these cells of AEP-deficient mice, the lamp-2-positive membrane structures were found to be greatly enlarged [19].
• In LAMP-2-deficient mice autophagic vacuoles accumulate in many tissues, including liver, pancreas, muscle, and heart [14].
• LAMP-1 and LAMP-2 also appeared to be present in low concentrations on Golgi trans-elements but were not detected in receptosomes marked by the presence of newly endocytosed alpha-2-macroglobulin, or in other cellular structures [20].
• The larger apparent molecular weights of the LAMP-2 glycoprotein and integrin glycoproteins alpha 5, alpha v and beta 1 in the transfected cells indicates that their oligosaccharide chains are substrates for GlcNAc-TV [21].

Analytical, diagnostic and therapeutic context of Lamp2

• In LAMP-2-deficient hepatocytes the half-life of both early and late autophagic vacuoles was prolonged as evaluated by quantitative electron microscopy [14].
• LAMP-2 was closely related or identical to the macrophage antigen, MAC-3, as indicated by antibody adsorption and tryptic peptide mapping [20].
• Complete absence of LAMP-2 was demonstrated by immunohistochemistry on the vacuolated skeletal and cardiac muscle, but also on the morphologically normal skeletal muscle [2].
• METHODS: In LAMP-2 deficient mice, we investigated cardiac function in vivo using Doppler-echocardiography and contractile function in vitro in isolated myocardial trabeculae [5].

References