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Lysosomal membrane proteomics and biogenesis of lysosomes

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Abstract

This review focuses on events involved in the biogenesis of the lysosome. This organelle contains a diverse array of soluble, luminal proteins capable of digesting all the macromolecules in the cell. Altered function of lysosomes or its constituent enzymes has been implicated in a host of human pathologies, including storage diseases, cancer, and infectious and neurodegenerative diseases. Luminal enzymes are well-characterized, and aspects of how they are incorporated into lysosomes are known. However, little is known about the composition of the membrane surrounding the organelle or how the membrane is assembled. Our starting point to study lysosome biogenesis is to define the composition of the membrane by the use of proven methods for purification of lysosomes to near homogeneity and then to characterize membrane-associated and integral lysosomal membrane proteins. This has been achieved using advanced proteomics (electrophoretic or chromatographic separations of proteins followed by time-of-flight mass spectrometric identification of peptide sequences). To date, we have identified 55 proteins in the membrane-associated fraction and 215 proteins in the integral membrane. By applying these methods to mouse models of lysosome dysgenesis (such as BEIGE, Pale Ear, PEARL) that are related to human diseases such as Chediak-Higashi and Hermansky-Pudlak syndromes, it may be possible to define the membrane protein composition of lysosomes in each of these mutants and to determine how they differ from normal. Identifying proteins affected in the respective mutants may provide hints about how they are targeted to the lysosomal membrane and how failure to target them leads to disease; these features are pivotal to understanding lysosome biogenesis and have the potential to implicate lysosomes in a broad range of human pathologies.

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References

  1. Derry D. M., Fawcett J. S., Andermann F., and Wolfe L. S. (1968). Late infantile systemic lipidosis: major monosialogangliosidosis, delineation of two types. Neurology 18, 340–348.

    PubMed  CAS  Google Scholar 

  2. Wolfe L. S., Callahan J., Fawcett J. S., Andermann F., and Scriver C. R. (1970). GM1-gangliosidosis without chrondrodystrophy or visceromegaly. Neurology 20, 23–44.

    Article  PubMed  CAS  Google Scholar 

  3. De Duve C. (1973). In: Lysosomes in Biology and Pathology, Vol. 1, Dingle J. T. and Fell H. B., eds., Amsterdam: North-Holland, pp. 3–40,

    Google Scholar 

  4. Ellgaard L. and Helenius A. (2003). Quality control in the endoplasmic reticulum. Nat. Rev. Molec. Cell Biol. 4, 181–191.

    Article  CAS  Google Scholar 

  5. Robinson M. S. (2004). Adaptable adaptors for coated vesicles. Trends Cell Biol. 14, 167–174.

    Article  PubMed  CAS  Google Scholar 

  6. Kornfeld S. and Mellman I. (1989). The biogenesis of lysosomes. Annu. Rev. Cell Biol. 5, 483–525.

    Article  PubMed  CAS  Google Scholar 

  7. Reitman M. L. and Kornfeld S. (1981). Lysosomal enzyme targeting. N-Acetylglucosaminyl-phosphotransferase selectively phosphorylates native lysosomal enzymes. J. Biol. Chem. 256, 11,977–11,980.

    CAS  Google Scholar 

  8. Hunziker W. and Geuze H. J. (1996). Intracellular trafficking of lysosomal membrane proteins. BioEssays 18, 379–389.

    Article  PubMed  CAS  Google Scholar 

  9. Reusch U., Bernhard O., Koszinowski U., and Schu P. (2002). AP-1A and AP-3A lysosomal sorting functions. Traffic 3, 752–761.

    Article  PubMed  CAS  Google Scholar 

  10. Eskelinen E. L., Tanaka Y., and Saftig P. (2003). At the acidic edge: emerging functions for lysosomal membrane proteins. Trends Cell Biol. 13, 137–145.

    Article  PubMed  CAS  Google Scholar 

  11. Rodionov D. G., Honing S., Silye A., Kongsvik T. L., Von Figura K., and Bakke O. (2002). Structural requirements for interaction between leucine-sorting signals and clathrin-associated adaptor protein complex AP3. J. Biol. Chem. 277, 47,436–47,443.

    CAS  Google Scholar 

  12. Hirst J. and Robinson M. S. (1998). Clathrin and adaptors. Biochim. Biophys. Acta. 1404, 173–193.

    Article  PubMed  CAS  Google Scholar 

  13. Le Borgne R., Alconada A., Bauer U., and Hoflack B. (1998). The mammalian AP-3 adaptor-like complex mediates the intracellular transport of lysosomal membrane glycoproteins. J. Biol. Chem. 273, 29,451–29,461.

    Article  Google Scholar 

  14. Boehm M., and Bonifacino J. S. (2002). Genetic analyses of adaptin function from yeast to mammals. Gene 286, 175–186.

    Article  PubMed  CAS  Google Scholar 

  15. Huizing M. and Gahl W. A. (2002). Disorders of vesicles of lysosomal lineage: the Hermansky-Pudlak syndromes. Curr. Molec. Med. 2, 451–467.

    Article  CAS  Google Scholar 

  16. Kornfeld S. (1990). Lysosomal enzyme targeting. Biochem. Soc. Trans. 18, 367–374.

    PubMed  CAS  Google Scholar 

  17. Finbow M. E., and Harrison M. A. (1997). The vacuolar H+-ATPase: a universal proton pump of eukaryotes. Biochem. J. 324, 697–712.

    PubMed  CAS  Google Scholar 

  18. Forgac M. (1996). Regulation of vacuolar acidification. Soc. Gen. Physiol. Series 51, 121–132.

    CAS  Google Scholar 

  19. Garin J., Diez R., Kieffer S., et al. (2001). The phagosome proteome: insight into phagosome functions. J Cell Biol 152, 165–180.

    Article  PubMed  CAS  Google Scholar 

  20. Jaiswal J. K., Chakrabarti S., Andrews N. W., and Siimon S. M. (2004). Synaptotagmin VII restricts fusion pore expansion during lysosomal exocytosis. PLoS Biol. 2, 1–9.

    Article  CAS  Google Scholar 

  21. Rao S. K., Huynh C., Proux-Gillardeaux V., Galli T., and Andrews N. W. (2004). Identification of SNAREs involved in Synaptotagmin vVII-regulated lysosomal exocytosis. J. Biol. Chem. 279, 20,471–20,479.

    CAS  Google Scholar 

  22. Morales C., Clermont Y., and Nadler N. J. (1986). Cyclic endocytic activity and kinetics of lysosomes in Sertoli cells of the rat: a morphometric analysis. Biol. Reprod. 34, 207–218.

    Article  PubMed  CAS  Google Scholar 

  23. Clermont Y., Morales C., and Hermo L. (1987). Endocytic activities of Sertoli cells in the rat. Ann. NY Acad. Sci. 513, 1–15.

    Article  PubMed  CAS  Google Scholar 

  24. Schmid S. L. (1997). Clathrin-coated vesicle formation and protein sorting: an integrated process. Ann. Rev. Biochem. 66, 511–548.

    Article  PubMed  CAS  Google Scholar 

  25. Kirchhausen T. (2000). Clathrin. Ann. Rev. Biochem. 69, 699–727.

    Article  PubMed  CAS  Google Scholar 

  26. Stephens L., Ellson C., and Hawkins P. (2002). Roles of PI3Ks in leukocyte chemotaxis and phagocytosis. Curr. Opin. Cell Biol. 14, 203–213.

    Article  PubMed  CAS  Google Scholar 

  27. Advani R. J., Yang B., Prekeris R., Lee K. C., Klumperman J., and Scheller R. H. (1999). VAMP-7 mediates vesicular transport from endosomes to lysosomes. J. Cell Biol. 146, 765–776.

    Article  PubMed  CAS  Google Scholar 

  28. Klionsky D. J. and Emr S. D. (2000). Autophagy as a regulated pathway of cellular degradation. Science 290, 1717–1721.

    Article  PubMed  CAS  Google Scholar 

  29. Suriapranata I., Epple U. D., Bernreuther D., Bredschneider M., Sovarasteanu K., and Thumm M. (2000). The breakdown of autophagic vesicles inside the vacuole depends on Aut4p. J. Cell Sci. 113, 4025–4033.

    PubMed  CAS  Google Scholar 

  30. Claus V., Jahraus A., Tjelle T., et al. (1998). Lysosomal enzyme trafficking between phagosomes, endosomes, and lysosomes in J774 macrophages. Enrichment of cathepsin H in early endosomes. J. Biol. Chem. 273, 9842–9851.

    Article  PubMed  CAS  Google Scholar 

  31. Kauppi M., Simonsen A., Bremnes B., et al. (2002). The small GTPase Rab22 interacts with EEA1 and controls endosomal membrane trafficking. J. Cell Sci. 115, 899–911.

    PubMed  CAS  Google Scholar 

  32. Callahan J. W. (1999). Molecular basis of GM1 gangliosidosis and Morquio disease, type B. Structure-function studies of lysosomal beta-galactosidase and the non- lysosomal beta-galactosidase-like protein. Biochim. Biophys. Acta. 1455, 85–103.

    PubMed  CAS  Google Scholar 

  33. Mahuran D. J. (1999). Biochemical consequences of mutations causing the GM2 gangliosidoses. Biochim. Biophys. Acta. 1455, 105–138.

    PubMed  CAS  Google Scholar 

  34. Bame K. J. and Rome L. H. (1985). Acetyl coenzyme A: alpha-glucosaminide N-acetyltransferase. Evidence for a transmembrane acetylation mechanism. J. Biol. Chem. 260, 11,293–11,299.

    CAS  Google Scholar 

  35. Shih V. E., Axel S. M., Tewksbury J. C., Watkins D., Cooper B. A., and Rosenblatt D. S. (1989). Defective lysosomal release of vitamin B12 (cb1F): A hereditary cobalamin metabolic disorder associated with sudden death. Am. J. Med. Genet. 33, 555–563.

    Article  PubMed  CAS  Google Scholar 

  36. Rosenblatt D. S., Hosack A., Matiaszuk N. V., Cooper B. A., and Laframboise R. (1985). Defect in vitamin B12 release from lysosomes: A newly described inborn error of vitamin B12 metabolism. Science 228, 1319–1321.

    Article  PubMed  CAS  Google Scholar 

  37. Carstea E. D., Morris J. A., Coleman K. G., et al. (1997). Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis. Science 277, 228–231.

    Article  PubMed  CAS  Google Scholar 

  38. Cruz J. C., Sugii S., Yu C., and Chang T. Y. (2000). Role of Niemann-Pick type C1 protein in intracellular trafficking of low density lipoproteinderived cholesterol. J. Biol. Chem. 275, 4013–4021.

    Article  PubMed  CAS  Google Scholar 

  39. Millat G., Marçais C., Tomasetto C., et al. (2001). Niemann-Pick C1 disease: Correlations between NPC1 mutations, levels of NPC1 protein, and phenotypes emphasize the functional significance of the putative sterol-sensing domain and of the cysteine-rich luminal loop. Am. J. Hum. Genet. 68, 1373–1385.

    Article  PubMed  CAS  Google Scholar 

  40. Aula N., Salomaki P., Timonen R., et al. (2000). The spectrum of SLC17A5-gene mutations resulting in free sialic acid-storage diseases indicates some genotype-phenotype correlation. Am. J. Hum. Genet. 67, 832–840.

    Article  PubMed  CAS  Google Scholar 

  41. Gahl W. A. (1987). Disorders of lysosomal membrane transport-cystinosis and Salla disease. Enzyme 38, 154–160.

    PubMed  CAS  Google Scholar 

  42. Kalatzis V., Cherqui S., Antignac C., and Gasnier B. (2001). Cystinosin, the protein defective in cystinosis, is a H+-driven lysosomal cystine transporter. EMBO J. 20, 5940–5949.

    Article  PubMed  CAS  Google Scholar 

  43. Phornphutkul C., Anikster Y., Huizing M., et al. (2001). The promoter of a lysosomal membrane transporter gene, CTNS, binds Sp-1, shares sequences with the promoter of an adjacent gene, carkl, and causes cystinosis if mutated in a critical region. Am. J. Hum. Genet. 69, 712–721.

    Article  PubMed  CAS  Google Scholar 

  44. Pearce D. A. (2000). Localization and processing of CLN3, the protein associated to Batten disease: where is it and what does it do? J. Neurosci. Res. 59, 19–23.

    Article  PubMed  CAS  Google Scholar 

  45. Savukoski M., Klockars T., Holmberg V., Santavuori P., Lander E. S., and Peltonen L. (1998). CLN5, a novel gene encoding a putative transmembrane protein mutated in Finnish variant late infantile neuronal ceroid lipofuscinosis. Nat. Genet. 19, 286–288.

    Article  PubMed  CAS  Google Scholar 

  46. Nishino I., Fu J., Tanji K., et al. (2000). Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature 406, 906–910.

    Article  PubMed  CAS  Google Scholar 

  47. Scimeca J. C., Quincey D., Parrinello H., et al. (2003). Novel mutations in the TCIRG1 gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis. Hum. Mutat. 21, 151–157.

    Article  PubMed  CAS  Google Scholar 

  48. Inaba K., Turley S., Iyoda T., et al. (2000). The formation of immunogenic major histocompatibility complex class II- peptide ligands in lysosomal compartments of dendritic cells is regulated by inflammatory stimuli. J. Exp. Med. 191, 927–936.

    Article  PubMed  CAS  Google Scholar 

  49. Zimmer K. P., Buning J., Weber P., Kaiserlian D., and Strobel S. (2000). Modulation of antigen trafficking to MHC class II-positive late endosomes of enterocytes. Gastroenterology 118, 128–137.

    Article  Google Scholar 

  50. Schroter C. J., Braun M., Englert J., Beck H., Schmid H., and Kalbacher H. (1999). A rapid method to separate endosomes from lysosomal contents using differential centrifugation and hypotonic lysis of lysosomes. J. Immunol. Meth. 227, 161–168.

    Article  CAS  Google Scholar 

  51. Künzli B. M., Berberat P. O., Zhu Z. W. W., et al. (2002). Influences of the lysosomal associated membrane proteins (Lamp-1, Lamp-2) and Mac-2 binding protein (Mac-2-BP) on the prognosis of pancreatic carcinoma. Cancer 94, 228–239.

    Article  PubMed  CAS  Google Scholar 

  52. Cabrita M. A., Hobman T. C., Hogue D. L., King K. M., and Cass C. E. (1999). Mouse transporter protein, a membrane protein that regulates cellular multidrug resistance, is localized to lysosomes. Cancer Res. 59, 4890–4897.

    PubMed  CAS  Google Scholar 

  53. Misasi R., Dionisi S., Farilla L., et al. (1997). Gangliosides and autoimmune diabetes. Diabetes Metab. Rev. 13, 163–179.

    Article  PubMed  CAS  Google Scholar 

  54. Ward D. M., Griffiths G. M., Stinchcombe J. C., and Kaplan J. (2000). Analysis of the lysosomal storage disease Chediak-Higashi syndrome. Traffic 1, 816–822.

    Article  PubMed  CAS  Google Scholar 

  55. Huizing M., Anikster Y., and Gahl W. A. (2001). Hermansky-Pudlak syndrome and Chediak-Higashi syndrome: Disorders of vesicle formation and trafficking. Thromb. Haemost. 86, 233–245.

    PubMed  CAS  Google Scholar 

  56. Spritz R. A. (1999). Multi-organellar disorders of pigmentation: intracellular traffic jams in mammals, flies and yeast. Trends Genet. 15, 337–340.

    Article  PubMed  CAS  Google Scholar 

  57. Dell’Angelica E. C., Mullins C., Caplan S., and Bonifacino J. S. (2000). Lysosome-related organelles. FASEB J. 14, 1265–1278.

    Article  PubMed  CAS  Google Scholar 

  58. Perou C. M., Leslie C. M., Green W., Li L., McVey-Ward D., and Kaplan J. (1997). The Beige/Chediak-Higashi syndrome gene encodes a widely expressed cytosolic protein. J. Biol. Chem. 272, 29,790–29,794.

    Article  CAS  Google Scholar 

  59. Barbosa M. D., Nguyen Q. A., Tchernev V. T., et al. (1996). Identification of the homologous beige and Chediak-Higashi syndrome genes [published erratum appears in Nature 1997 Jan 2;385(6611):97]. Nature 382, 262–265.

    Article  PubMed  CAS  Google Scholar 

  60. Setaluri V. (2000). Sorting and targeting of melanosomal membrane proteins: signals, pathways, and mechanisms. Pigment Cell Res. 13, 128–134.

    Article  PubMed  CAS  Google Scholar 

  61. Harris E., Wang N., Wu Wl W. L., Weatherford A., De Lozanne A., and Cardelli J. (2002). Dictyostelium LvsB mutants model the lysosomal defects associated with Chediak-Higashi syndrome. Molec. Biol. Cell 13, 656–669.

    Article  PubMed  CAS  Google Scholar 

  62. Huizing M., Scher C. D., Strovel E., et al. (2002). Nonsense mutations in ADTB3A cause complete deficiency of the b3A subunit of adaptor complex-3 and severe Hermansky-Pudlak syndrome type 2. Pediat. Res. 51, 150–158.

    Article  PubMed  CAS  Google Scholar 

  63. Falcon-Perez J. M., Starcevic M., Gautam R., and Dell’Angelica E. C. (2002). BLOC-1, a novel complex containing the Pallidin and Muted proteins in the biogenesis of melanosomes and platelet-dense granules. J. Biol. Chem. 277, 28,191–28,199.

    Article  CAS  Google Scholar 

  64. Feng L. J., Novak E. K., Hartnell L. M., Bonifacino J. S., Collinson L. M., and Swank R. T. (2002). The Hermansky-Pudlak syndrome 1 (HPS1) and HPS2 genes independently contribute to the production and function of platelet dense granules, melanosomes, and lysosomes. Blood 99, 1651–1658.

    Article  PubMed  CAS  Google Scholar 

  65. Simmen T., Schmidt A., Hunziker A., and Beermann F. (1999). The tyrosinase tail mediates sorting to the lysosomal compartment in MDCK cells via a di-leucine and a tyrosine-based signal. J. Cell. Sci. 112, 45–53.

    PubMed  CAS  Google Scholar 

  66. Shiba T., Takatsu H., Nogi T., et al. (2002). Structural basis for recognition of acidic-cluster dileucine sequence by GGA1. Nature 415, 937–941.

    Article  PubMed  CAS  Google Scholar 

  67. Misra S., Puertollano R., Kato Y., Bonifacino J. S., and Hurley J. H. (2002). Structural basis for acidic-cluster-dileucine sorting-signal recognition by VHS domains. Nature 415, 933–937.

    Article  PubMed  CAS  Google Scholar 

  68. Stahn R., Maier K. -P., and Hannig K. (1970). A new method for the preparation of rat liver lysosomes. Separation of cell organelles of rat liver by carrier-free continuous electrophoresis. J. Cell Biol. 46, 576–591.

    Article  PubMed  CAS  Google Scholar 

  69. Canut H., Bauer J., and Weber G. (1999). Separation of plant membranes by electromigration techniques. J. Chromatog. B., Biomed. Sci. Applic. 722, 121–139.

    Article  CAS  Google Scholar 

  70. Volkl A. and Mohr H. (1999). Peroxisome subpopulations of the rat liver. Isolation by immune free flow electrophoresis. J. Histochem. Cytochem. 47, 1111–1118

    PubMed  CAS  Google Scholar 

  71. Bagshaw R. D., Pasternak S. H., Mahuran D. J., and Callahan J. W. (2003). Nicastrin is a resident lysosomal membrane protein. Biochem. Biophys. Res. Commun. 300, 615–618.

    Article  PubMed  CAS  Google Scholar 

  72. Pasternak S. H., Bagshaw R. D., Guiral M., et al. (2003). Presenilin-1, Nicastrin, Amyloid Precursor Protein, and gamma-secretase activity are co-localized in the lysosomal membrane. J. Biol. Chem. 278, 26,687–26,694.

    Article  CAS  Google Scholar 

  73. Chataway T. K., Whittle A. M., Lewis M. D., et al. (1998). Development of a two-dimensional gel electrophoresis database of human lysosomal proteins. Electrophoresis 19, 834–836.

    Article  PubMed  CAS  Google Scholar 

  74. Journet A., Chapel A., Kieffer S., Louwagie M., Luche S., and Garin J. (2000). Towards a human repertoire of monocytic lysosomal proteins. Electrophoresis 21, 3411–3419.

    Article  PubMed  CAS  Google Scholar 

  75. Bagshaw R., Callahan J. W., and Mahuran D. (2000). Lysosomal proteomics using 2D-gels and mass spectrometry. J. Inher. Metab. Dis. 23, 214.

    Google Scholar 

  76. Beruter J., Colombo J. P., and Bachmann C. (1978). Purification and properties of arginase from human liver and erythrocytes. Biochem. J. 175, 449–454.

    PubMed  CAS  Google Scholar 

  77. Lu M., Sautin Y. Y., Holliday L. S., and Gluck S. L. (2004). The glycolytic enzyme aldolase mediates assembly, expression, and activity of vacuolar H+-ATPase. J. Biol. Chem. 279, 8732–8739.

    Article  PubMed  CAS  Google Scholar 

  78. Chevallet M., Santoni V., Poinas A., et al. (1998). New zwitterionic detergents improve the analysis of membrane proteins by two-dimensional electrophoresis. Electrophoresis 19, 1901–1909.

    Article  PubMed  CAS  Google Scholar 

  79. Hippler M., Klein J., Fink A., Allinger T., and Hoerth P. (2001). Towards functional proteomics of membrane protein complexes: analysis of thylakoid membranes from Chlamydomonas reinhardtii. Plant J. 28, 595–606.

    Article  PubMed  CAS  Google Scholar 

  80. Bagshaw R. D., Mahuran D. J., and Callahan J. W. (2005). A proteomics analysis of lysosomal integral-membrane proteins reveals the diverse composition of the organelle. Molec. Cell Proteom. 4, 133–143.

    Article  CAS  Google Scholar 

  81. Dell’Angelica E. C. (2003). Melanosome biogenesis: shedding light on the origin of an obscure organelle. Trends Cell Biol. 13, 503–506.

    Article  PubMed  CAS  Google Scholar 

  82. Di Pietro S. M., Falcon-Perez J. M., and Dell’Angelica E. C. (2004). Characterization of BLOC-2, a complex containing the Hermansky-Pudlak syndrome proteins HPS3, HPS5 and HPS6. Traffic 5, 276–283.

    Article  PubMed  CAS  Google Scholar 

  83. Nazarian R., Falcon-Perez J. M., and Dell’Angelica E. C. (2004). Biogenesis of lysosome-related organelles complex 3 (BLOC-3): a complex containing the Hermansky-Pudlak syndrome (HPS) proteins HPS1 and HPS4. Proc. Natl. Acad. Sci. USA 100, 8770–8775.

    Article  CAS  Google Scholar 

  84. Verhoeven K., De Jonghe P., Coen K., et al. (2003). Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy. Am. J. Hum. Genet. 72, 722–727.

    Article  PubMed  CAS  Google Scholar 

  85. Pfeffer S. (2003). Membrane domains in the secretory and endocytic pathways. Cell 112, 507–517.

    Article  PubMed  CAS  Google Scholar 

  86. Pasqualato S., Renault L., and Cherfils J. (2002). Arf, Arl, Arp and Sar proteins: a family of GTP-binding proteins with a structural device for ‘front-back’ communication. EMBO Reports 3, 1035–1041.

    Article  PubMed  CAS  Google Scholar 

  87. Vernoud V., Horton A. C., Yang Z., and Nielsen E. (2003). Analysis of the small GTPase gene superfamily of Arabidopsis. Plant Physiol. 131, 1191–1208.

    Article  PubMed  CAS  Google Scholar 

  88. Riederer M. A., Soldati T., Shapiro A. D., Lin J., and Pfeffer S. R. (1994). Lysosome biogenesis requires Rab9 function and receptor recycling from endosomes to the trans-Golgi network. J. Cell Biol. 125, 573–582.

    Article  PubMed  CAS  Google Scholar 

  89. Lombardi D., Soldati T., Riederer M. A., Goda Y., Zerial M., and Pfeffer S. R. (1993). Rab9 functions in transport between late endosomes and the trans Golgi network. EMBO J 12, 677–682.

    PubMed  CAS  Google Scholar 

  90. Arai K., Yoshida S., Naito S., and Ohkuma S. (2002). GTPgammaS-stimulated lysosomal lysis dependent of the assembly of adaptor proteins on lysosome. Biol. Pharm. Bull. 25, 1125–1128.

    Article  PubMed  CAS  Google Scholar 

  91. Sai Y., Matsuda T., Arai K., and Ohkuma S. (1998). Disintegration of lysosomes mediated by GTPgammaS-treated cytosol: possible involvement of phospholipases. J. Biochem. (Tokyo) 123, 630–636.

    CAS  Google Scholar 

  92. Jones D. H., Bax B., Fensome A., and Cockcroft S. (1999). ADP ribosylation factor 1 mutants identify a phospholipase D effector region and reveal that phospholipase D participates in lysosomal secretion but is not sufficient for recruitment of coatomer I. Biochem. J. 341, 185–192.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Research Institute, The Hospital for Sick Children, Canada

    Richard D. Bagshaw, Don J. Mahuran & John W. Callahan

  2. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

    Richard D. Bagshaw & Don J. Mahuran

  3. Department of Biochemistry, University of Toronto, Toronto, Canada

    John W. Callahan

  4. Department of Pediatrics, University of Toronto, Toronto, Canada

    John W. Callahan

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  1. Richard D. Bagshaw
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Bagshaw, R.D., Mahuran, D.J. & Callahan, J.W. Lysosomal membrane proteomics and biogenesis of lysosomes. Mol Neurobiol 32, 27–41 (2005). https://doi.org/10.1385/MN:32:1:027

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