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Disease relevance of Lysosomes


Psychiatry related information on Lysosomes


High impact information on Lysosomes

  • Capture of antigenic peptides by class II MHC molecules is facilitated because antigen catabolism and class II MHC maturation take place in the same compartments or in communicating compartments of the endosome/lysosome system [7].
  • Morphological and biochemical work suggests that internalization of the receptor-insulin complex from the plasma membrane transfers insulin to intracellular organelles like the lysosomes, the Golgi apparatus, or nucleus, where degradation by insulin protease takes place, whereas the receptor is recycled back to the membrane [8].
  • Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous disease involving abnormalities of melanosomes, platelet dense granules and lysosomes [9].
  • Moreover, we provide pharmacological and biochemical evidence that this Ca(2+) store is the reserve granule, the functional equivalent of a lysosome in the sea urchin egg [10].
  • Using an HRP-Wingless fusion protein to track the fate of endocytosed Wingless, we show that degradation by targeting to lysosomes is one such strategy [11].

Chemical compound and disease context of Lysosomes


Biological context of Lysosomes


Anatomical context of Lysosomes

  • A specific receptor on the surface of cultured human fibroblasts binds plasma low density lipoprotein (LDL) with high affinity, and thereby initiates a cellular process by which the LDL is internalized and degraded within lysosomes and its cholesterol component is made available for cellular membrane synthesis [22].
  • In macrophages lacking TACO, mycobacteria were readily transported to lysosomes followed by their degradation [23].
  • This protein, termed TACO, represents a component of the phagosome coat that is normally released prior to phagosome fusion with or maturation into lysosomes [23].
  • Addition of BFA to cells resulted in the tubulation of the endosomal system, the trans-Golgi network (TGN), and lysosomes [24].
  • The movement of LEP100 from endosomes to lysosomes was blocked by chloroquine, causing redistribution to a new steady state in which about 30% of LEP100 molecules were localized in clathrin-coated patches on the cell surface, while intracellular LEP100 occurred in nearby endocytic vesicles [25].

Associations of Lysosomes with chemical compounds

  • Cycling of the integral membrane glycoprotein, LEP100, between plasma membrane and lysosomes: kinetic and morphological analysis [25].
  • Liposome-encapsulated antigens are processed in lysosomes, recycled, and presented to T cells [26].
  • The 14C-sucrose-labeled peptides that arose upon degradation of the added 14C-sucBSA polylysine accumulated exclusively within lysosomes [27].
  • M6P residues on oligosaccharides of newly synthesized lysosomal enzymes are essential for efficient receptor-mediated transport to lysosomes [28].
  • The delivery of soluble hydrolases to lysosomes is mediated by the cation-independent and cation-dependent mannose 6-phosphate receptors [29].

Gene context of Lysosomes

  • In lymphoblastoid cells homozygous for these same HLA-DRB1 alleles the constitutive 70-kD HSP, HSP73, that targets selected proteins to lysosomes coprecipitated with HLA-DR [30].
  • Thus, SNX1 is likely to play a role in sorting EGFR to lysosomes [31].
  • TLR9 signals after translocating from the ER to CpG DNA in the lysosome [32].
  • TSG101 UEV-ubiquitin interactions are therefore important for delivery of both substrates and hydrolytic enzymes to lysosomes, which receive proteins via fusion with MVBs [33].
  • Overexpression of SNX3 alters endosomal morphology and delays transport to the lysosome [34].

Analytical, diagnostic and therapeutic context of Lysosomes


  1. Hermansky-Pudlak syndrome is caused by mutations in HPS4, the human homolog of the mouse light-ear gene. Suzuki, T., Li, W., Zhang, Q., Karim, A., Novak, E.K., Sviderskaya, E.V., Hill, S.P., Bennett, D.C., Levin, A.V., Nieuwenhuis, H.K., Fong, C.T., Castellan, C., Miterski, B., Swank, R.T., Spritz, R.A. Nat. Genet. (2002) [Pubmed]
  2. Nef-induced CD4 degradation: a diacidic-based motif in Nef functions as a lysosomal targeting signal through the binding of beta-COP in endosomes. Piguet, V., Gu, F., Foti, M., Demaurex, N., Gruenberg, J., Carpentier, J.L., Trono, D. Cell (1999) [Pubmed]
  3. Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles. Oh, J., Bailin, T., Fukai, K., Feng, G.H., Ho, L., Mao, J.I., Frenk, E., Tamura, N., Spritz, R.A. Nat. Genet. (1996) [Pubmed]
  4. Identification of the homologous beige and Chediak-Higashi syndrome genes. Barbosa, M.D., Nguyen, Q.A., Tchernev, V.T., Ashley, J.A., Detter, J.C., Blaydes, S.M., Brandt, S.J., Chotai, D., Hodgman, C., Solari, R.C., Lovett, M., Kingsmore, S.F. Nature (1996) [Pubmed]
  5. Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells. Tollefson, A.E., Hermiston, T.W., Lichtenstein, D.L., Colle, C.F., Tripp, R.A., Dimitrov, T., Toth, K., Wells, C.E., Doherty, P.C., Wold, W.S. Nature (1998) [Pubmed]
  6. Niemann-Pick Type C disease and Alzheimer's disease: the APP-endosome connection fattens up. Nixon, R.A. Am. J. Pathol. (2004) [Pubmed]
  7. Capture and processing of exogenous antigens for presentation on MHC molecules. Watts, C. Annu. Rev. Immunol. (1997) [Pubmed]
  8. Insulin receptors: binding kinetics and structure-function relationship of insulin. Gammeltoft, S. Physiol. Rev. (1984) [Pubmed]
  9. Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6. Zhang, Q., Zhao, B., Li, W., Oiso, N., Novak, E.K., Rusiniak, M.E., Gautam, R., Chintala, S., O'Brien, E.P., Zhang, Y., Roe, B.A., Elliott, R.W., Eicher, E.M., Liang, P., Kratz, C., Legius, E., Spritz, R.A., O'Sullivan, T.N., Copeland, N.G., Jenkins, N.A., Swank, R.T. Nat. Genet. (2003) [Pubmed]
  10. NAADP mobilizes Ca(2+) from reserve granules, lysosome-related organelles, in sea urchin eggs. Churchill, G.C., Okada, Y., Thomas, J.M., Genazzani, A.A., Patel, S., Galione, A. Cell (2002) [Pubmed]
  11. Regulated endocytic routing modulates wingless signaling in Drosophila embryos. Dubois, L., Lecourtois, M., Alexandre, C., Hirst, E., Vincent, J.P. Cell (2001) [Pubmed]
  12. Cyclic beta-1,2-glucan is a Brucella virulence factor required for intracellular survival. Arellano-Reynoso, B., Lapaque, N., Salcedo, S., Briones, G., Ciocchini, A.E., Ugalde, R., Moreno, E., Moriyón, I., Gorvel, J.P. Nat. Immunol. (2005) [Pubmed]
  13. The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes. Horwitz, M.A. J. Exp. Med. (1983) [Pubmed]
  14. Studies on the defect underlying the lysosomal storage of sialic acid in Salla disease. Lysosomal accumulation of sialic acid formed from N-acetyl-mannosamine or derived from low density lipoprotein in cultured mutant fibroblasts. Renlund, M., Kovanen, P.T., Raivio, K.O., Aula, P., Gahmberg, C.G., Ehnholm, C. J. Clin. Invest. (1986) [Pubmed]
  15. Effect of hepatic vitamin A depletion on the liver in humans and rats. Leo, M.A., Sato, M., Lieber, C.S. Gastroenterology (1983) [Pubmed]
  16. The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin. Lefrancois, S., Zeng, J., Hassan, A.J., Canuel, M., Morales, C.R. EMBO J. (2003) [Pubmed]
  17. Nef induces CD4 endocytosis: requirement for a critical dileucine motif in the membrane-proximal CD4 cytoplasmic domain. Aiken, C., Konner, J., Landau, N.R., Lenburg, M.E., Trono, D. Cell (1994) [Pubmed]
  18. Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes. Reddy, A., Caler, E.V., Andrews, N.W. Cell (2001) [Pubmed]
  19. Late endosomes derive from early endosomes by maturation. Stoorvogel, W., Strous, G.J., Geuze, H.J., Oorschot, V., Schwartz, A.L. Cell (1991) [Pubmed]
  20. Primary structure of bovine thyroglobulin deduced from the sequence of its 8,431-base complementary DNA. Mercken, L., Simons, M.J., Swillens, S., Massaer, M., Vassart, G. Nature (1985) [Pubmed]
  21. Transmembrane molecular pump activity of Niemann-Pick C1 protein. Davies, J.P., Chen, F.W., Ioannou, Y.A. Science (2000) [Pubmed]
  22. Regulation of the activity of the low density lipoprotein receptor in human fibroblasts. Brown, M.S., Goldstein, J.L. Cell (1975) [Pubmed]
  23. A coat protein on phagosomes involved in the intracellular survival of mycobacteria. Ferrari, G., Langen, H., Naito, M., Pieters, J. Cell (1999) [Pubmed]
  24. Brefeldin A's effects on endosomes, lysosomes, and the TGN suggest a general mechanism for regulating organelle structure and membrane traffic. Lippincott-Schwartz, J., Yuan, L., Tipper, C., Amherdt, M., Orci, L., Klausner, R.D. Cell (1991) [Pubmed]
  25. Cycling of the integral membrane glycoprotein, LEP100, between plasma membrane and lysosomes: kinetic and morphological analysis. Lippincott-Schwartz, J., Fambrough, D.M. Cell (1987) [Pubmed]
  26. Liposome-encapsulated antigens are processed in lysosomes, recycled, and presented to T cells. Harding, C.V., Collins, D.S., Slot, J.W., Geuze, H.J., Unanue, E.R. Cell (1991) [Pubmed]
  27. The selective degradation of injected proteins occurs principally in the cytosol rather than in lysosomes. Bigelow, S., Hough, R., Rechsteiner, M. Cell (1981) [Pubmed]
  28. Mucolipidosis II is caused by mutations in GNPTA encoding the alpha/beta GlcNAc-1-phosphotransferase. Tiede, S., Storch, S., Lübke, T., Henrissat, B., Bargal, R., Raas-Rothschild, A., Braulke, T. Nat. Med. (2005) [Pubmed]
  29. Sorting of mannose 6-phosphate receptors mediated by the GGAs. Puertollano, R., Aguilar, R.C., Gorshkova, I., Crouch, R.J., Bonifacino, J.S. Science (2001) [Pubmed]
  30. HLA-DR4 and HLA-DR10 motifs that carry susceptibility to rheumatoid arthritis bind 70-kD heat shock proteins. Auger, I., Escola, J.M., Gorvel, J.P., Roudier, J. Nat. Med. (1996) [Pubmed]
  31. Enhanced degradation of EGF receptors by a sorting nexin, SNX1. Kurten, R.C., Cadena, D.L., Gill, G.N. Science (1996) [Pubmed]
  32. TLR9 signals after translocating from the ER to CpG DNA in the lysosome. Latz, E., Schoenemeyer, A., Visintin, A., Fitzgerald, K.A., Monks, B.G., Knetter, C.F., Lien, E., Nilsen, N.J., Espevik, T., Golenbock, D.T. Nat. Immunol. (2004) [Pubmed]
  33. Ubiquitin recognition by the human TSG101 protein. Sundquist, W.I., Schubert, H.L., Kelly, B.N., Hill, G.C., Holton, J.M., Hill, C.P. Mol. Cell (2004) [Pubmed]
  34. SNX3 regulates endosomal function through its PX-domain-mediated interaction with PtdIns(3)P. Xu, Y., Hortsman, H., Seet, L., Wong, S.H., Hong, W. Nat. Cell Biol. (2001) [Pubmed]
  35. Phagosome-lysosome fusion. Characterization of intracellular membrane fusion in mouse macrophages. Kielian, M.C., Cohn, Z.A. J. Cell Biol. (1980) [Pubmed]
  36. An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation. Agarraberes, F.A., Terlecky, S.R., Dice, J.F. J. Cell Biol. (1997) [Pubmed]
  37. Identification of two lysosomal membrane glycoproteins. Chen, J.W., Murphy, T.L., Willingham, M.C., Pastan, I., August, J.T. J. Cell Biol. (1985) [Pubmed]
  38. Interaction of rat liver lysosomal membranes with actin. Mehrabian, M., Bame, K.J., Rome, L.H. J. Cell Biol. (1984) [Pubmed]
  39. An endogenous MDCK lysosomal membrane glycoprotein is targeted basolaterally before delivery to lysosomes. Nabi, I.R., Le Bivic, A., Fambrough, D., Rodriguez-Boulan, E. J. Cell Biol. (1991) [Pubmed]
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