Biogenesis of Melanosomes

Melanins and Melanosomes: Biosynthesis, Biogenesis, Physiological, and Pathological Functions

Volumn , Issue , 2011, Pages 247-294

  Delevoye, Cédric ^a   Giordano, Francesca ^a   Marks, Michael S ^b   Raposo, Graça ^a  

^a INSTITUT CURIE   (France)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Chediak Higashi syndrome; Endocytosis; Griscelli syndrome; Hermansky Pudlak syndrome; Lysosome related organelle; Melanin; Melanocyte; Melanosome; Physiological amyloid; Pmel

Indexed keywords

EID: 84876812822     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527636150.ch9     Document Type: Chapter

References (237)

1. King, R.A., Hearing, V.J., Creel, D.J., and Oetting, W.S. (1995) Albinism, in The Metabolic and Molecular Bases of Inherited Disease, vol. III (eds C.R. Scriver, A.L. Beaudet, W.S. Sly, and D. Valle), McGraw-Hill, New York, pp. 4353-4392
2. Marmorstein, A.D., Finnemann, S.C., Bonilha, V.L., and Rodriguez-Boulan, E. (1998) Morphogenesis of the retinal pigment epithelium: toward understanding retinal degenerative diseases. Ann. NY Acad. Sci., 857, 1-12
3. Carr, R.E. and Siegel, I.M. (1979) The retinal pigment epithelium in ocular albinism, in The Retinal Pigment Epithelium (eds K.M. Zinn and M.P. Marmar), Harvard University Press, Cambridge, MA, pp. 413-423
4. Orlow, S.J. (1995) Melanosomes are specialized members of the lysosomal lineage of organelles. J. Invest. Dermatol., 105, 3-7
5. Raposo, G., Tenza, D., Murphy, D.M., Berson, J.F., and Marks, M.S. (2001) Distinct protein sorting and localization to premelanosomes, melanosomes, and lysosomes in pigmented melanocytic cells. J. Cell Biol., 152, 809-824
6. Marks, M.S. and Seabra, M.C. (2001) The melanosome: membrane dynamics in black and white. Nat. Rev. Mol. Cell Biol., 2, 738-748
7. Raposo, G. and Marks, M.S. (2007) Melanosomes-dark organelles enlighten endosomal membrane transport. Nat. Rev. Mol. Cell Biol., 8, 786-797
8. Huizing, M., Helip-Wooley, A., Westbroek, W., Gunay-Aygun, M., and Gahl, W.A. (2008) Disorders of lysosome-related organelle biogenesis: clinical and molecular genetics. Annu. Rev. Genomics Hum. Genet., 9, 359-386
9. Birbeck, M.S.C., Mercer, E.H., and Barnicot, N.A. (1956) The structure and formation of pigment granules in human hair. Exp. Cell Res., 10, 505-514
10. Seiji, M., Fitzpatrick, T.M., Simpson, R.T., and Birbeck, M.S.C. (1963) Chemical composition and terminology of specialized organelles (melanosomes and melanin granules) in mammalian melanocytes. Nature, 197, 1082-1084
11. Hurbain, I., Geerts, W.J., Boudier, T., Marco, S., Verkleij, A.J., Marks, M.S., and Raposo, G. (2008) Electron tomography of early melanosomes: implications for melanogenesis and the generation of fi brillar amyloid sheets. Proc. Natl. Acad. Sci. USA, 10519726-31, 19726-19731
12. Moyer, F.H. (1966) Genetic variations in the fi ne structure and ontogeny of mouse melanin granules. Am. Zool., 6, 43-66
13. Lamoreux, M.L., Delmas, V., Larue, L., and Bennett, D.C. (2010) The Colors of Mice: A Model Genetic Network, Wiley-Blackwell, Oxford
14. Lopes, V.S., Wasmeier, C., Seabra, M.C., and Futter, C.E. (2007) Melanosome maturation defect in Rab38-defi cient retinal pigment epithelium results in instability of immature melanosomes during transient melanogenesis. Mol. Biol. Cell, 18, 3914-3927
15. Miyamoto, M. and Fitzpatrick, T.B. (1957) On the nature of the pigment in retinal pigment epithelium. Science, 126, 449-450
16. Smith-Thomas, L., Richardson, P., Thody, A.J., Graham, A., Palmer, I., Flemming, L., Parsons, M.A., Rennie, I.G., and MacNeil, S. (1996) Human ocular melanocytes and retinal pigment epithelial cells differ in their melanogenic properties in vivo and in vitro. Curr. Eye Res., 15, 1079-1091
17. Schraermeyer, U., Kopitz, J., Peters, S., Henke-Fahle, S., Blitgen-Heinecke, P., Kokkinou, D., Schwarz, T., and Bartz-Schmidt, K.U. (2006) Tyrosinase biosynthesis in adult mammalian retinal pigment epithelial cells. Exp. Eye Res., 83, 315-321
18. Gwynn, B., Ciciotte, S.L., Hunter, S.J., Washburn, L.L., Smith, R.S., Andersen, S.G., Swank, R.T., Dell'Angelica, E.C., Bonifacino, J.S., Eicher, E.M., et al. (2000) Defects in the cappuccino (cno) gene on mouse chromosome 5 and human 4p cause Hermansky-Pudlak syndrome by an AP-3-independent mechanism. Blood, 96, 4227-4235
19. Biesemeier, A., Kreppel, F., Kochanek, S., and Schraermeyer, U. (2010) The classical pathway of melanogenesis is not essential for melanin synthesis in the adult retinal pigment epithelium. Cell Tissue Res., 339, 551-560
20. Novikoff, A.B., Albala, A., and Biempica, L. (1968) Ultrastructural and cytochemical observations on B-16 and Harding-Passey mouse melanomas. The origin of premelanosomes and compound melanosomes. J. Histochem. Cytochem., 16, 299-319
21. Seiji, M. and Kikuchi, A. (1969) Acid phosphatase activity in melanosomes. J. Invest. Dermatol., 52, 212-216
22. Zhou, B.-K., Boissy, R.E., Pifko-Hirst, S., Moran, D.J., and Orlow, S.J. (1993) Lysosome-associated membrane protein-1 (LAMP-1) is the melanocyte vesicular membrane glycoprotein band II. J. Invest. Dermatol., 100, 110-114
23. Diment, S., Eidelman, M., Rodriguez, G.M., and Orlow, S.J. (1995) Lysosomal hydrolases are present in melanosomes and are elevated in melanizing cells. J. Biol. Chem., 270, 4213-4215
24. Bennett, D.C. and Lamoreux, M.L. (2003) The color loci of mice-a genetic century. Pigment Cell Res., 16, 333-344
25. Theos, A.C., Truschel, S.T., Raposo, G., and Marks, M.S. (2005) The Silver locus product Pmel17/gp100/Silv/ME20: controversial in name and in function. Pigment Cell Res., 18, 322-336
26. Ganesan, A.K., Ho, H., Bodemann, B., Petersen, S., Aruri, J., Koshy, S., Richardson, Z., Le, L.Q., Krasieva, T., Roth, M.G., et al. (2008) Genome-wide siRNA-based functional genomics of pigmentation identifi es novel genes and pathways that impact melanogenesis in human cells. PLoS Genet., 4, e1000298
27. Kushimoto, T., Basrur, V., Valencia, J., Matsunaga, J., Vieira, W.D., Ferrans, V.J., Muller, J., Appella, E., and Hearing, V.J. (2001) A model for melanosome biogenesis based on the purifi cation and analysis of early melanosomes. Proc. Natl. Acad. Sci. USA, 98, 10698-10703
28. Theos, A.C., Tenza, D., Martina, J.A., Hurbain, I., Peden, A.A., Sviderskaya, E.V., Stewart, A., Robinson, M.S., Bennett, D.C., Cutler, D.F., et al. (2005) Functions of AP-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes. M ol. Biol. Cell, 16, 5356-5372
29. Lerner, A.B., Fitzpatrick, T.B., Calkins, E., and Summerson, W.H. (1949) Mammalian tyrosinase: preparation and properties. J. Biol. Chem., 178, 185-195
30. K ö rner, A. and Pawelek, J. (1982) Mammalian tyrosinase catalyzes three reactions in the biosynthesis of melanin. Science, 217, 1163-1165
31. Medigeshi, G.R. and Schu, P. (2003) Characterization of the in vitro retrograde transport of MPR46. Traffi c, 4, 802-811
32. Solano, F., Jimenez-Cervantes, C., Martinez-Liarte, J.H., Garcia-Borron, J.C., Jara, J.R., and Lozano, J.A. (1996) Molecular mechanism for catalysis by a new zinc-enzyme, dopachrome tautomerase. B iochem. J., 313, 447-453
33. Kobayashi, T., Urabe, K., Winder, A., Jim é nez-Cervantes, C., Imokawa, G., Brewington, T., Solano, F., Garc í a -Borr ó n, J.C., and Hearing, V.J. (1994) Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in melanin biosynthesis. EMBO J., 13, 5818-5825
34. Sarangarajan, R. and Boissy, R.E. (2001) Tyrp1 and oculocutaneous albinism type 3. Pigment Cell Res., 14, 437-444
35. Kobayashi, T., Imokawa, G., Bennett, D.C., and Hearing, V.J. (1998) Tyrosinase stabilization by Tyrp1 (the brown locus protein). J. Biol. Chem., 273, 31801-31805
36. Hearing, V.J. (1999) Biochemical control of melanogenesis and melanosomal organization. J. Invest. Dermatol. Symp. Proc., 4, 24-28
37. Blagoveshchenskaya, A.D., Hewitt, E.W., and Cutler, D.F. (1999) Di-leucine signals mediate targeting of tyrosinase and synaptotagmin to synaptic-like microvesicles within PC12 cells. Mol. Biol. Cell, 10, 3979-3990
38. Calvo, P.A., Frank, D.W., Bieler, B.M., Berson, J.F., and Marks, M.S. (1999) A cytoplasmic sequence in human tyrosinase defi nes a second class of di-leucine-based sorting signals for late endosomal and lysosomal delivery. J. Biol. Chem., 274, 12780-12789
39. Vijayasaradhi, S., Xu, Y., Bouchard, B., and Houghton, A.N. (1995) Intracellular sorting and targeting of melanosomal membrane proteins: identifi cation of signals for sorting of the human brown locus protein, gp75. J. Cell Biol., 130, 807-820
40. Honing, S., Sandoval, I.V., and von Figura, K. (1998) A di-leucine-based motif in the cytoplasmic tail of LIMP-II and tyrosinase mediates selective binding of AP-3. EMBO J., 17, 1304-1314
41. Simmen, T., Schmidt, A., Hunziker, W., 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
42. Basrur, V., Yang, F., Kushimoto, T., Higashimoto, Y., Yasumoto, K., Valencia, J., Muller, J., Vieira, W.D., Watabe, H., Shabanowitz, J., et al. (2003) Proteomic analysis of early melanosomes: identifi cation of novel melanosomal proteins. J. Proteome Res., 2, 69-79
43. Chi, A., Valencia, J.C., Hu, Z.Z., Watabe, H., Yamaguchi, H., Mangini, N.J., Huang, H., Canfi eld, V.A., Cheng, K.C., Yang, F., et al. (2006) Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. J. Proteome Res., 5, 3135-3144
44. Sitaram, A., Piccirillo, R., Palmisano, I., Harper, D.C., Dell'Angelica, E.C., Schiaffi no, M.V., and Marks, M.C. (2009) Localization to mature melanosomes by virtue of cytoplasmic dileucine motifs is required for human OCA2 function. Mol. Biol. Cell, 29, 1464-1477
45. Innamorati, G., Piccirillo, R., Bagnato, P., Palmisano, I., and Schiaffi no, M.V. (2006) The melanosomal/lysosomal protein OA1 has properties of a G protein-coupled receptor. Pigment Cell Res., 19, 125-135
46. Rinchik, E.M., Bultman, S.J., Horsthemke, B., Lee, S.T., Strunk, K.M., Spritz, R.A., Avidano, K.M., Jong, M.T., and Nicholls, R.D. (1993) A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism. Nature, 361, 72-76
47. Orlow, S.J. and Brilliant, M.H. (1999) The pink-eyed dilution locus controls the biogenesis of melanosomes and levels of melanosomal proteins in the eye. Exp. Eye Res., 68, 147-154
48. Rosemblat, S., Sviderskaya, E.V., Easty, D.J., Wilson, A., Kwon, B.S., Bennett, D.C., and Orlow, S.J. (1998) Melanosomal defects in melanocytes from mice lacking expression of the pink-eyed dilution gene: correction by culture in the presence of excess tyrosine. E xp. Cell Res., 239, 344-352
49. Chen, K., Manga, P., and Orlow, S.J. (2002) Pink-eyed dilution protein controls the processing of tyrosinase. Mol. Biol. Cell, 13, 1953-1964
50. Costin, G.-E., Valencia, J.C., Vieira, W.D., Lamoreux, M.L., and Hearing, V.J. (2003) Tyrosinase processing and intracellular traffi cking is disrupted in mouse primary melanocytes carrying the underwhite (uw) mutation. A model for oculocutaneous albinism (OCA) type 4. J. Cell Sci., 116, 3203-3212
51. Puri, N., Gardner, J.M., and Brilliant, M.H. (2000) Aberrant pH of melanosomes in pink-eyed dilution (p) mutant melanocytes. J. Invest. Dermatol., 115, 607-613
52. Brilliant, M. and Gardner, J. (2001) Melanosomal pH, pink locus protein and their roles in melanogenesis. J. Invest. Dermatol., 117, 386-387
53. Chen, K., Minwalla, L., Ni, L., and Orlow, S.J. (2004) Correction of defective early tyrosinase processing by bafi lomycin A1 and monensin in pink-eyed dilution melanocytes. Pigment Cell Res., 17, 36-42
54. Manga, P., Boissy, R.E., Pifko-Hirst, S., Zhou, B.K., and Orlow, S.J. (2001) Mislocalization of melanosomal proteins in melanocytes from mice with oculocutaneous albinism type 2. Exp. Eye Res., 72, 695-710
55. Schiaffi no, M.V., Baschirotto, C., Pellegrini, G., Montalti, S., Tacchetti, C., De Luca, M., and Ballabio, A. (1996) The ocular albinism type 1 gene product is a membrane glycoprotein localized to melanosomes. Proc. Natl. Acad. Sci. USA, 93, 9055-9060
56. Lopez, V.M., Decatur, C.L., Stamer, W.D., Lynch, R.M., and McKay, B.S. (2008) l-DOPA is an endogenous ligand for OA1. PLoS Biol., 6, e236
57. Giordano, F., Bonetti, C., Surace, E.M., Marigo, V., and Raposo, G. (2009) The ocular albinism type 1 (OA1) G-protein coupled receptor functions with MART-1 at early stages of melanogenesis to control melanosome identity and composition. Hum. Mol. Genet., 18, 4530-4545
58. Ginger, R.S., Askew, S.E., Ogborne, R.M., Wilson, S., Ferdinando, D., Dadd, T., Smith, A.M., Kazi, S., Szerencsei, R.T., Winkfein, R.J., et al. (2008) SLC24A5 encodes a trans-Golgi network protein with potassium-dependent sodium-calcium exchange activity that regulates human epidermal melanogenesis. J. Biol. Chem., 283, 5486-5495
59. Brilliant, M. (2005) Oculocutaneous Albinism Type 4, GeneReviews, Seattle, WA
60. Lamason, R.L., Mohideen, M.-A.P.K., Mest, J.R., Wong, A.C., Norton, H.L., Aros, M.C., Jurynec, M.J., Mao, X., Humphreville, V.R., Humbert, J.E., et al. (2005) SLC24A5, a putative cation exchanger, affects pigmentation in zebrafi sh and humans. Science, 310, 1782-1786
61. Newton, J.M., Cohen-Barak, O., Hagiwara, N., Gardner, J.M., Davisson, M.T., King, R.A., and Brilliant, M.H. (2001) Mutations in the human orthologue of the mouse underwhite gene (uw) underlie a new form of oculocutaneous albinism, OCA4. Am. J. Hum. Genet., 69, 981-988
62. Oancea, E., Vriens, J., Brauchi, S., Jun, J., Splawski, I., and Clapham, D.E. (2009) TRPM1 forms ion channels associated with melanin content in melanocytes. Sci. Signal., 2, ra21
63. McNeill, M.S., Paulsen, J., Bonde, G., Burnight, E., Hsu, M.Y., and Cornell, R.A. (2007) Cell death of melanophores in zebrafi sh trpm7 mutant embryos depends on melanin synthesis. J. Invest. Dermatol., 127, 2020-2030
64. Hoashi, T., Watabe, H., Muller, J., Yamaguchi, Y., Vieira, W.D., and Hearing, V.J. (2005) MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes. J. Biol. Chem., 280, 14006-14016
65. Setty, S.R., Tenza, D., Sviderskaya, E.V., Bennett, D.C., Raposo, G., and Marks, M.S. (2008) Cell-specifi c ATP7A transport sustains copper-dependent tyrosinase activity in melanosomes. Nature, 454, 1142-1146
66. Lutsenko, S., Barnes, N.L., Bartee, M.Y., and Dmitriev, O.Y. (2007) Function and regulation of human copper -transporting ATPases. Physiol. Rev., 87, 1011-1046
67. Silvers, W.K. (1979) The Coat Colors of Mice: A Model for Mammalian Gene Action and Interaction, Springer, New York
68. Maxfi eld, F.R. and McGraw, T.E. (2004) Endocytic recycling. Nat. Rev. Mol. Cell Biol., 5, 121-132
69. Gruenberg, J. (2001) The endocytic pathway: a mosaic of domains. Nat. Rev. Mol. Cell Biol., 2, 721-730
70. Gould, G.W. and Lippincott-Schwartz, J. (2009) New roles for endosomes: from vesicular carriers to multi-purpose platforms. N at. Rev. Mol. Cell Biol., 10, 287-292
71. Doherty, G.J. and McMahon, H.T. (2009) Mechanisms of endocytosis. Annu. Rev. Biochem., 78, 857-902
72. Jovic, M., Sharma, M., Rahajeng, J., and Caplan, S. (2010) The early endosome: a busy sorting station for proteins at the crossroads. H istol. Histopathol., 25, 99-112
73. Simonsen, A., Lippe, R., Christoforidis, S., Gaullier, J.M., Brech, A., Callaghan, J., Toh, B.H., Murphy, C., Zerial, M., and Stenmark, H. (1998) EEA1 links PI 3 K function to Rab5 regulation of endosome fusion. Nature, 394, 494-498
74. van Ijzendoorn, S.C. (2006) Recycling endosomes. J. Cell Sci., 119, 1679-1681
75. Stenmark, H. (2009) Rab GTPases as coordinators of vesicle traffi c. Nat. Rev. Mol. Cell., 10, 513-525
76. Piper, R.C. and Katzmann, D.J. (2007) Biogenesis and function of multivesicular bodies. Annu. Rev. Cell Dev. Biol., 23, 519-547
77. Sachse, M., Urbe, S., Oorschot, V., Strous, G.J., and Klumperman, J. (2002) Bilayered clathrin coats on endosomal vacuoles are involved in protein sorting toward lysosomes. Mol. Biol. Cell, 13, 1313-1328
78. Raiborg, C. and Stenmark, H. (2009) The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature, 458, 445-452
79. Hurley, J.H. (2010) The ESCRT complexes. Crit. Rev. Biochem. Mol. Biol., 45, 463-487
80. Pryor, P.R. and Luzio, J.P. (2009) Delivery of endocytosed membrane proteins to the lysosome. Biochim. Biophys. Acta, 1793, 615-624
81. White, I.J., Bailey, L.M., Aghakhani, M.R., Moss, S.E., and Futter, C.E. (2006) EGF stimulates annexin 1-dependent inward vesiculation in a multivesicular endosome subpopulation. EMBO J., 25, 1-12
82. Simons, M. and Raposo, G. (2009) Exosomes-vesicular carriers for intercellular communication. Curr. Opin. Cell Biol., 21, 575-581
83. Turner, W.A., Jr, Taylor, J.D., and Tchen, T.T. (1975) Melanosome formation in the goldfi sh: the role of multivesicular bodies. J. Ultrastruct. Res., 51, 16-31
84. Jimbow, K., Oikawa, O., Sugiyama, S., and Takeuchi, T. (1979) Comparison of eumelanogenesis in retinal and follicular melanocytes; role of vesiculo-globular bodies in melanosome differentiation. J. Invest. Dermatol., 73, 278-284
85. Maul, G.G. and Brumbaugh, J.A. (1971) On the possible function of coated vesicles in melanogenesis of the regenerating fowl feather. J. Cell Biol., 48, 41-48
86. Bouchard, B., Fuller, B.B., Vijayasaradhi, S., and Houghton, A.N. (1989) Induction of pigmentation in mouse fi broblasts by expression of human tyrosinase cDNA. J. Exp. Med., 169, 2029-2042
87. Raposo, G., Marks, M.S., and Cutler, D.F. (2007) Lysosome-related organelles: driving post-Golgi compartments into specialisation. Curr. Opin. Cell Biol., 19, 394-401
88. Stinchcombe, J., Bossi, G., and Griffi ths, G.M. (2004) Linking albinism and immunity: the secrets of secretory lysosomes. Science, 305, 55-59
89. Wei, M.L. (2006) Hermansky-Pudlak syndrome: a disease of protein traffi cking and organelle function. Pigment Cell Res., 19, 19-42
90. Boissy, R.E., Moellmann, G.E., and Halaban, R. (1987) Tyrosinase and acid phosphatase activities in melanocytes from avian albinos. J. Invest. Dermatol., 88, 292-300
91. Anderson, R.G.W., Falck, J.R., Goldstein, J.L., and Brown, M.S. (1984) Visualization of acidic organelles in intact cells by electron microscopy. Proc. Natl. Acad. Sci. USA, 81, 4838-4842
92. Fujita, H., Sasano, E., Yasunaga, K., Furuta, K., Yokota, S., Wada, I., and Himeno, M. (2001) Evidence for distinct membrane traffi c pathways to melanosomes and lysosomes in melanocytes. J. Investig. Dermatol. Symp. Proc., 6, 19-24
93. Schraermeyer, U. (1995) Transport of endocytosed material into melanin granules in cultured choroidal melanocytes of cattle-new insights into the relationship of melanosomes with lysosomes. Pigment Cell Res., 8, 209-214
94. Orlow, S.J., Boissy, R.E., Moran, D.J., and Pifko-Hirst, S. (1993) Subcellular distribution of tyrosinase and tyrosinase -related protein-1: implications for melanosomal biogenesis. J. Invest. Dermatol., 100, 55-64
95. Seiji, M. and Iwashia, S. (1965) Intracellular localization of tyrosinase and site of melanin formation in melanocyte. J. Invest. Dermatol., 45, 305-314
96. Saeki, H. and Oikawa, A. (1978) Effects of pH and type of sugar in the medium on tyrosinase activity in cultured melanoma cells. J. Cell Physiol., 94, 139-145
97. Devi, C.C., Tripathi, R.K., and Ramaiah, A. (1987) pH-dependent interconvertible allosteric forms of murine melanoma tyrosinase. Physiological implications. Eur. J. Biochem., 166, 705-711
98. Berson, J.F., Harper, D., Tenza, D., Raposo, G., and Marks, M.S. (2001) Pmel17 initiates premelanosome morphogenesis within multivesicular bodies. Mol. Biol. Cell, 12, 3451-3464
99. Piccirillo, R., Palmisano, I., Innamorati, G., Bagnato, P., Altimare, D., and Schiaffi no, M.V. (2006) An unconventional dileucine-based motif and a novel cytosolic motif are required for the lysosomal and melanosomal targeting of OA1. J. Cell Sci., 119, 2003-2014
100. Furumura, M., Sakai, C., Potterf, S.B., Vieira, W.D., Barsh, G.S., and Hearing, V.J. (1998) Characterization of genes modulated during pheomelanogenesis using differential display. Proc. Natl. Acad. Sci. USA, 95, 7374-7378
101. Kobayashi, T., Vieira, W.D., Potterf, B., Sakai, C., Imokawa, G., and Hearing, V.J. (1995) Modulation of melanogenic protein expression during the switch from eu-to pheomelanogenesis. J. Cell Sci., 108, 2301-2309
102. Schraermeyer, U. and Heimann, K. (1999) Current understanding on the role of retinal pigment epithelium and its pigmentation. Pigment Cell Res., 12, 219-236
103. Schraermeyer, U., Peters, S., Thumann, G., Kociok, N., and Heimann, K. (1999) Melanin granules of retinal pigment epithelium are connected with the lysosomal degradation pathway. Exp. Eye Res., 68, 237-245
104. Nichols, S.E., Harper, D.C., Berson, J.F., and Marks, M.S. (2003) A novel splice variant of Pmel17 expressed by human melanocytes and melanoma cells lacking some of the internal repeats. J. Invest. Dermatol., 121, 821-830
105. Bailin, T., Lee, S.T., and Spritz, R.A. (1996) Genomic organization and sequence of D12S53E (Pmel 17), the human homologue of the mouse silver (si) locus. J. Invest. Dermatol., 106, 24-27
106. Chakraborty, A.K., Platt, J.T., Kim, K.K., Kwon, B.S., Bennett, D.C., and Pawelek, J.M. (1996) Polymerization of 5,6-dihydroxyindole-2-carboxylic acid to melanin by the pmel 17/ silver locus protein. Eur. J. Biochem., 236, 180-188
107. Adema, G.J., de Boer, A.J., Vogel, A.M., Loenen, W.A., and Figdor, C.G. (1994) Molecular characterization of the melanocyte lineage-specifi c antigen gp100. J. Biol. Chem., 269, 20126-20133
108. Hoashi, T., Muller, J., Vieira, W.D., Rouzaud, F., Kikuchi, K., Tamaki, K., and Hearing, V.J. (2006) The repeat domain of the melanosomal matrix protein PMEL17/GP100 is required for the formation of organellar fi bers. J. Biol. Chem., 281, 21198-21208
109. Hoashi, T., Sato, S., Yamaguchi, Y., Passeron, T., Tamaki, K., and Hearing, V.J. (2010) Glycoprotein nonmetastatic melanoma protein b, a melanocytic cell marker, is a melanosome-specifi c and proteolytically released protein. FASEB J., 24, 1616-1629
110. Wagner, S.N., Wagner, C., Schultewolter, T., and Goos, M. (1997) Analysis of Pmel17/gp100 expression in primary human tissue specimens: implications for melanoma immuno -and gene-therapy. Cancer Immunol. Immunother., 44, 239-247
111. Cormier, J.N., Abati, A., Fetsch, P., Hijazi, Y.M., Rosenberg, S.A., Marincola, F.M., and Topalian, S.L. (1998) Comparative analysis of the in vivo expression of tyrosinase, MART-1/ Melan-A, and gp100 in metastatic melanoma lesions: implications for immunotherapy. J. Immunother., 21, 27-31
112. Folpe, A.L., Goodman, Z.D., Ishak, K.G., Paulino, A.F., Taboada, E.M., Meehan, S.A., and Weiss, S.W. (2000) Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres: a novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults. Am. J. Surg. Pathol., 24, 1239-1246
113. Matsumoto, Y., Horiba, K., Usuki, J., Chu, S.C., Ferrans, V.J., and Moss, J. (1999) Markers of cell proliferation and expression of melanosomal antigen in lymphangioleiomyomatosis. A m. J. Respir. Cell Mol. Biol., 21, 327-336
114. Lee, Z.H., Hou, L., Moellmann, G., Kuklinska, E., Antol, K., Fraser, M., Halaban, R., and Kwon, B.S. (1996) Characterization and subcellular localization of human Pmel 17/ silver, a 100-kDa (pre)melanosomal membrane protein associated with 5,6-dihydroxyindole-2-carboxylic acid (DHICA) converting activity. J. Invest. Dermatol., 106, 605-610
115. Orlow, S.J., Zhou, B.-K., Boissy, R.E., and Pifko-Hirst, S. (1993) Identifi cation of a mammalian melanosomal matrix glycoprotein. J. Invest. Dermatol., 101, 141-144
116. Zhou, B.K., Kobayashi, T., Donatien, P.D., Bennett, D.C., Hearing, V.J., and Orlow, S.J. (1994) Identifi cation of a melanosomal matrix protein encoded by the murine si (silver) locus using " organelle scanning ". Proc. Natl. Acad. Sci. USA, 91, 7076-7080
117. Berson, J.F., Theos, A.C., Harper, D.C., Tenza, D., Raposo, G., and Marks, M.S. (2003) Proprotein convertase cleavage liberates a fi brillogenic fragment of a resident glycoprotein to initiate melanosome biogenesis. J. Cell Biol., 161, 521-533
118. Donatien, P.D. and Orlow, S.J. (1995) Interaction of melanosomal proteins with melanin. Eur. J. Biochem., 232, 159-164
119. Theos, A.C., Berson, J.F., Theos, S.C., Herman, K.E., Harper, D.C., Tenza, D., Sviderskaya, E.V., Lamoreux, M.L., Bennett, D.C., Raposo, G., et al. (2006) Dual loss of ER export and endocytic signals with altered melanosome morphology in the silver mutation of Pmel17. Mol. Biol. Cell, 17, 3598-3612
120. Fowler, D.M., Koulov, A.V., Alory-Jost, C., Marks, M.S., Balch, W.E., and Kelly, J.W. (2006) Functional amyloid formation within mammalian tissue. PLoS Biol., 4, e6
121. Watt, B., van Niel, G., Fowler, D.M., Hurbain, I., Luk, K.C., Stayrook, S.E., Lemmon, M.A., Raposo, G., Shorter, J., Kelly, J.W., et al. (2009) N-terminal domains elicit formation of functional Pmel17 amyloid fi brils. J. Biol. Chem., 284, 35543-35555
122. Chiti, F. and Dobson, C.M. (2006) Protein misfolding,functional amyloid and human disease. Annu. Rev. Biochem., 75, 333-366
123. Fowler, D.M., Koulov, A.V., Balch, W.E., and Kelly, J.W. (2007) Functional amyloid-from bacteria to humans. Trends Biochem. Sci., 32, 217-223
124. Watt, B., Raposo, G., and Marks, M.S. (2010) Pmel17: an amyloid determinant of organelle structure, in Functional Amyloid Aggregation (ed. M. Bucciantini), Research Signpost, Trivandrum
125. Esclamado, R.M., Gown, A.M., and Vogel, A.M. (1986) Unique proteins defi ned by monoclonal antibodies specifi c for human melanoma. Am. J. Surg., 152, 376-385
126. Gown, A.M., Vogel, A.M., Hoak, D., Gough, F., and McNutt, M.A. (1986) Monoclonal antibodies specifi c for melanocytic tumors distinguish subpopulations of melanocytes. Am. J. Pathol., 123, 195-203
127. Chiamenti, A.M., Vella, F., Bonetti, F., Pea, M., Ferrari, S., Martignoni, G., Benedetti, A., and Suzuki, H. (1996) Anti-melanoma monoclonal antibody HMB-45 on enhanced chemiluminescence-western blotting recognizes a 30-35 kDa melanosome -associated sialated glycoprotein. Melanoma Res., 6, 291-298
128. Kapur, R.P., Bigler, S.A., Skelly, M., and Gown, A.M. (1992) Anti-melanoma monoclonal antibody HMB45 identifi es an oncofetal glycoconjugate associated with immature melanosomes. J. Histochem. Cytochem., 40, 207-212
129. Harper, D.C., Theos, A.C., Herman, K.E., Tenza, D., Raposo, G., and Marks, M.S. (2008) Premelanosome amyloid-like fi brils are composed of only Golgi -processed forms of pmel17 that have been proteolytically processed in endosomes. J. Biol. Chem., 283, 2307-2322
130. Lepage, S. and Lapointe, R. (2006) Melanosomal targeting sequences from gp100 are essential for MHC class II-restricted endogenous epitope presentation and mobilization to endosomal compartments. Cancer Res., 66, 2423-2432
131. Robila, V., Ostankovitch, M., Altrich -Vanlith, M.L., Theos, A.C., Drover, S., Marks, M.S., Restifo, N., and Engelhard, V.H. (2008) MHC class II presentation of gp100 epitopes in melanoma cells requires the function of conventional endosomes and is infl uenced by melanosomes. J. Immunol., 181, 7843-7852
132. Kummer, M.P., Maruyama, H., Huelsmann, C., Baches, S., Weggen, S., and Koo, E.H. (2009) Formation of pmel17 amyloid is regulated by juxtamembrane metalloproteinase cleavage, and the resulting C-terminal fragment is a substrate for γ-secretase. J. Biol. Chem., 284, 2296-2306
133. Maresh, G.A., Marken, J.S., Neubauer, M., Aruffo, A., Hellstr ö m, I., Hellstr ö m, K.E., and Marquardt, H. (1994) Cloning and expression of the gene for the melanoma-associated ME20 antigen. DNA Cell Biol., 13, 87-95
134. Hoashi, T., Tamaki, K., and Hearing, V.J. (2010) The secreted form of a melanocyte membrane-bound glycoprotein (Pmel17/gp100) is released by ectodomain shedding. FASEB J., 24, 916-930
135. De Strooper, B., Vassar, R., and Golde, T. (2010) The secretases: enzymes with therapeutic potential in Alzheimer disease. Nat. Rev. Neurol., 6, 99-107
136. McGlinchey, R.P., Shewmaker, F., McPhie, P., Monterroso, B., Thurber, K., and Wickner, R.B. (2009) The repeat domain of the melanosome fi bril protein Pmel17 forms the amyloid core promoting melanin synthesis. Proc. Natl. Acad. Sci. USA, 106, 13731-13736
137. Futter, C.E., Ramalho, J.S., Jaissle, G.B., Seeliger, M.W., and Seabra, M.C. (2004) The role of Rab27a in the regulation of melanosome distribution within retinal pigment epithelial cells. Mol. Biol. Cell, 15, 2264-2275
138. Dunn, L.C. and Thigpen, L.W. (1930) The silver mouse: a recessive color variation. J. Hered., 21, 495
139. Bassi, M.T., Schiaffi no, M.V., Renieri, A., De Nigris, F., Galli, L., Bruttini, M., Gebbia, M., Bergen, A.A., Lewis, R.A., and Ballabio, A. (1995) Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome. Nat. Genet., 10, 13-19
140. Schiaffi no, M.V., d'Addio, M., Alloni, A., Baschirotto, C., Valetti, C., Cortese, K., Puri, C., Bassi, M.T., Colla, C., De Luca, M., et al. (1999) Ocular albinism: evidence for a defect in an intracellular signal transduction system. Nat. Genet., 23, 108-112
141. Cortese, K., Giordano, F., Surace, E.M., Venturi, C., Ballabio, A., Tacchetti, C., and Marigo, V. (2005) The ocular albinism type 1 (OA1) gene controls melanosome maturation and size. Invest. Ophthalmol. Vis. Sci., 46, 4358-4364
142. Incerti, B., Cortese, K., Pizzigoni, A., Surace, E.M., Varani, S., Coppola, M., Jeffery, G., Seeliger, M., Jaissle, G., Bennett, D.C., et al. (2000) Oa1 knock-out: new insights on the pathogenesis of ocular albinism type 1. Hum. Mol. Genet., 9, 2781-2788
143. Young, A., Powelson, E.B., Whitney, I.E., Raven, M.A., Nusinowitz, S., Jiang, M., Birnbaumer, L., Reese, B.E., and Farber, D.B. (2008) Involvement of OA1, an intracellular GPCR, and G alpha i3, its binding protein, in melanosomal biogenesis and optic pathway formation. Invest. Ophthalmol. Vis. Sci., 49, 3245-3252
144. Blander, J.M. (2007) Coupling Toll-like receptor signaling with phagocytosis: potentiation of antigen presentation. Trends Immunol., 28, 19-25
145. Palmisano, I., Bagnato, P., Palmigiano, A., Innamorati, G., Rotondo, G., Altimare, D., Venturi, C., Sviderskaya, E.V., Piccirillo, R., Coppola, M., et al. (2008) The ocular albinism type 1 protein, an intracellular G protein -coupled receptor, regulates melanosome transport in pigment cells. Hum. Mol. Genet., 17, 3487-3501
146. Schiaffi no, M.V. (2010) Signaling pathways in melanosome biogenesis and pathology. I nt. J. Biochem. Cell Biol., 42, 1094-1104
147. Theos, A.C., Truschel, S.T., Tenza, D., Hurbain, I., Harper, D.C., Berson, J.F., Thomas, P.C., Raposo, G., and Marks, M.S. (2006) A lumenal domain -dependent pathway for sorting to intralumenal vesicles of multivesicular endosomes involved in organelle morphogenesis. Dev. Cell, 10, 343-354
148. Kovacs, G.G., Gelpi, E., Str ö bel, T., Ricken, G., Nyengaard, J.R., Bernheimer, H., and Budka, H. (2007) Involvement of the endosomal-lysosomal system correlates with regional pathology in Creutzfeldt-Jakob disease. J. Neuropathol. Exp. Neurol., 66, 628-636
149. Maul, G.G. (1969) Golgi-melanosome relationship in human melanoma in vitro. J. Ultrastruct. Res., 26, 163-176
150. Kobayashi, T., Urabe, K., Orlow, S.J., Higashi, K., Imokawa, G., Kwon, B.S., Potterf, B., and Hearing, V.J. (1994) The Pmel 17/silver locus protein. Characterization and investigation of its melanogenic function. J. Biol. Chem., 269, 29198-29205
151. Yasumoto, K., Watabe, H., Valencia, J.C., Kushimoto, T., Kobayashi, T., Appella, E., and Hearing, V.J. (2004) Epitope mapping of the melanosomal matrix protein gp100 (PMEL17): rapid processing in the endoplasmic reticulum and glycosylation in the early Golgi compartment. J. Biol. Chem., 279, 28330-28338
152. Valencia, J.C., Rouzaud, F., Julien, S., Chen, K.G., Passeron, T., Yamaguchi, Y., Abu-Asab, M., Tsokos, M., Costin, G.E., Yamaguchi, H., et al. (2007) Sialylated core 1 O-glycans infl uence the sorting of Pmel17/gp100 and determine its capacity to form fi brils. J. Biol. Chem., 282, 11266-11280
153. Valencia, J.C., Hoashi, T., Pawelek, J.M., Solano, F., and Hearing, V.J. (2006) Pmel17: controversial indeed but critical to melanocyte function. Pigment Cell Res., 19, 250-252; author reply 253-257
154. Gagnon, E., Duclos, S., Rondeau, C., Chevet, E., Cameron, P.H., Steele -Mortimer, O., Paiement, J., Bergeron, J.J., and Desjardins, M. (2002) Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages. Cell, 110, 119-131
155. L é vy, F., Muehlethaler, K., Salvi, S., Peitrequin, A.-L., Lindholm, C.K., Cerottini, J.-C., and Rimoldi, D. (2005) Ubiquitylation of a melanosomal protein by HECT-E3 ligases serves as sorting signal for lysosomal degradation. Mol. Biol. Cell, 16, 1777-1787
156. Truschel, S.T., Simoes, S., Setty, S.R.G., Harper, D.C., Tenza, T., Thomas, P.C., Herman, K.E., Sackett, S.D., Cowan, D.C., Theos, A.C., et al. (2009) ESCRT-I function is required for Tyrp-1 transport from early endosomes to the melanosome limiting membrane. Traffi c, 10, 1318-1336
157. Trajkovic, K., Hsu, C., Chiantia, S., Rajendran, L., Wenzel, D., Wieland, F., Schwille, P., Brugger, B., and Simons, M. (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science, 319, 1244-1247
158. Arvan, P. and Castle, D. (1998) Sorting and storage during secretory granule biogenesis: looking backward and looking forward. Biochem. J., 332, 593-610
159. Gibson, A., Futter, C.E., Maxwell, S., Allchin, E.H., Shipman, M., Kraehenbuhl, J.P., Domingo, D., Odorizzi, G., Trowbridge, I.S., and Hopkins, C.R. (1998) Sorting mechanisms regulating membrane protein traffi c in the apical transcytotic pathway of polarized MDCK cells. J. Cell Biol., 143, 81-94
160. Gruenberg, J. and Maxfi eld, F.R. (1995) Membrane transport in the endocytic pathway. Curr. Opin. Cell Biol., 7, 552-563
161. Bright, N.A., Gratian, M.J., and Luzio, J.P. (2005) Endocytic delivery to lysosomes mediated by concurrent fusion and kissing events in living cells. Curr. Biol., 15, 360-365
162. Delevoye, C., Hurbain, I., Tenza, D., Sibarita, J.-B., Uzan-Gafsou, S., Ohno, H., Geerts, W.J.C., Verkleij, A.J., Salamero, J., Marks, M.S., et al. (2009) AP-1 and KIF13A coordinate endosomal sorting and positioning during melanosome biogenesis. J. Cell Biol., 187, 247-264
163. Seabra, M.C. and Coudrier, E. (2004) Rab GTPases and myosin motors in organelle motility. Traffi c, 5, 393-399
164. Van Den Bossche, K., Naeyaert, J.M., and Lambert, J. (2006) The quest for the mechanism of melanin transfer. Traffi c, 7, 769-778
165. Perou, C.M., Moore, K.J., Nagle, D.L., Misumi, D.J., Woolf, E.A., McGrail, S.H., Holmgren, L., Brody, T.H., Dussault, B.J., Jr, Monroe, C.A., et al. (1996) Identifi cation of the murine beige gene by YAC complementation and positional cloning. Nat. Genet., 13, 303-308
166. 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., et al. (1996) Identifi cation of the homologous beige and Chediak-Higashi syndrome genes. Nature, 382, 262-265
167. Ward, D.M., Shifl ett, S.L., Huynh, D., Vaughn, M.B., Prestwich, G., and Kaplan, J. (2003) Use of expression constructs to dissect the functional domains of the CHS/beige protein: identifi cation of multiple phenotypes. Traffi c, 4, 403-415
168. Faigle, W., Raposo, G., Tenza, D., Pinet, V., Vogt, A.B., Kropshofer, H., Fischer, A., de Saint-Basile, G., and Amigorena, S. (1998) Defi cient peptide loading and MHC class II endosomal sorting in a human genetic immunodefi ciency disease: the Chediak-Higashi syndrome. J. Cell Biol., 141, 1121-1134
169. Gautam, R., Novak, E.K., Tan, J., Wakamatsu, K., Ito, S., and Swank, R.T. (2006) Interaction of Hermansky-Pudlak syndrome genes in the regulation of lysosome-related organelles. T raffi c, 7, 779-792
170. Di Pietro, S.M. and Dell'Angelica, E.C. (2005) The cell biology of Hermansky-Pudlak syndrome: recent advances. Traffi c, 6, 525-533
171. Swank, R.T., Novak, E.K., McGarry, M.P., Zhang, Y., Li, W., Zhang, Q., and Feng, L. (2000) Abnormal vesicular traffi cking in mouse models of Hermansky-Pudlak syndrome. P igment Cell Res., 13, 59-67
172. Ohno, H. (2006) Cell science at a glance: clathrin-associated adaptor protein complexes. J. Cell Sci., 119, 3719-3721
173. Dell'Angelica, E.C., Shotelersuk, V., Aguilar, R.C., Gahl, W.A., and Bonifacino, J.S. (1999) Altered traffi cking of lysosomal proteins in Hermansky-Pudlak syndrome due to mutations in the β 3A subunit of the AP-3 adaptor. Mol. Cell, 3, 11-21
174. Feng, L., Seymour, A.B., Jiang, S., To, A., Peden, A.A., Novak, E.K., Zhen, L., Rusiniak, M.E., Eicher, E.M., Robinson, M.S., et al. (1999) The beta3A subunit gene (Ap3b1) of the AP-3 adaptor complex is altered in the mouse hypopigmentation mutant pearl, a model for Hermansky-Pudlak syndrome and night blindness. Hum. Mol. Genet., 8, 323-330
175. Kantheti, P., Qiao, X., Diaz, M.E., Peden, A.A., Meyer, G.E., Carskadon, S.L., Kapfhamer, D., Sufalko, D., Robinson, M.S., Noebels, J.L., et al. (1998) Mutation in AP-3 β in the mocha mouse links endosomal transport to storage defi ciency in platelets, melanosomes, and synaptic vesicles. Neuron, 21, 111-122
176. Nguyen, T., Novak, E.K., Kermani, M., Fluhr, J., Peters, L.L., Swank, R.T., and Wei, M.L. (2002) Melanosome morphologies in murine models of Hermansky-Pudlak syndrome refl ect blocks in organelle development. J. Invest. Dermatol., 119, 1156-1164
177. Nguyen, T. and Wei, M.L. (2004) Characterization of melanosomes in murine Hermansky-Pudlak syndrome: mechanisms of hypopigmentation. J. Invest. Dermatol., 122, 452-460
178. Huizing, M., Sarangarajan, R., Strovel, E., Zho, Y., Gahl, W.A., and Boissy, R.E. (2001) AP-3 mediates tyrosinase but not TRP-1 traffi cking in human melanocytes. M ol. Biol. Cell, 12, 2075-2085
179. Dell'Angelica, E.C., Klumperman, J., Stoorvogel, W., and Bonifacino, J.S. (1998) Association of the AP-3 adaptor complex with clathrin. Science, 280, 431-434
180. Peden, A.A., Oorschot, V., Hesser, B.A., Austin, C.D., Scheller, R.H., and Klumperman, J. (2004) Localization of the AP-3 adaptor complex defi nes a novel endosomal exit site for lysosomal membrane proteins. J. Cell Biol., 164, 1065-1076
181. Di Pietro, S.M., Falcon-Perez, J.M., Tenza, D., Setty, S.R., Marks, M.S., Raposo, G., and Dell'Angelica, E.C. (2006) BLOC-1 interacts with BLOC-2 and the AP-3 complex to facilitate protein traffi cking on endosomes. Mol. Biol. Cell, 17, 4027-4038
182. Zizioli, D., Meyer, C., Guhde, G., Saftig, P., von Figura, K., and Schu, P. (1999) Early embryonic death of mice defi cient in gamma-adaptin. J. Biol. Chem., 274, 5385-5390
183. Meyer, C., Zizioli, D., Lausmann, S., Eskelinen, E.L., Hamann, J., Saftig, P., von Figura, K., and Schu, P. (2000) mu1A-adaptin-defi cient mice: lethality, loss of AP-1 binding and rerouting of mannose 6-phosphate receptors. EMBO J., 19, 2193-2203
184. Chapuy, B., Tikkanen, R., Muhlhausen, C., Wenzel, D., von Figura, K., and Honing, S. (2008) AP-1 and AP-3 mediate sorting of melanosomal and lysosomal membrane proteins into distinct post-Golgi traffi cking pathways. Traffi c, 9, 1157-1172
185. Lakkaraju, A., Carvajal-Gonzalez, J.M., and Rodriguez-Boulan, E. (2009) It takes two to tango to the melanosome. J. Cell Biol., 187, 161-163
186. Dell'Angelica, E.C. (2004) The building BLOC(k)s of lysosomes and related organelles. Curr. Opin. Cell Biol., 16, 458-464
187. Setty, S.R., Tenza, D., Truschel, S.T., Chou, E., Sviderskaya, E.V., Theos, A.C., Lamoreux, M.L., Di Pietro, S.M., Starcevic, M., Bennett, D.C., et al. (2007) BLOC-1 is required for cargo-specifi c sorting from vacuolar early endosomes toward lysosome-related organelles. Mol. Biol. Cell, 18, 768-780
188. Moriyama, K. and Bonifacino, J.S. (2002) Pallidin is a component of a multi -protein complex involved in the biogenesis of lysosome-related organelles. Traffi c, 3, 666-677
189. Ghiani, C.A., Starcevic, M., Rodriguez -Fernandez, I.A., Nazarian, R., Cheli, V.T., Chan, L.N., Malvar, J.S., de Vellis, J., Sabatti, C., and Dell'Angelica, E.C. (2010) The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth. Mol. Psychiatry, 15, 204-215
190. Ilardi, J.M., Mochida, S., and Sheng, Z.H. (1999) Snapin: a SNARE-associated protein implicated in synaptic transmission. Nat. Neurosci., 2, 119-124
191. Salazar, G., Craige, B., Styers, M.L., Newell-Litwa, K.A., Doucette, M.M., Wainer, B.H., Falcon-Perez, J.M., Dell'Angelica, E.C., Peden, A.A., Werner, E., et al. (2006) BLOC-1 complex defi ciency alters the targeting of adaptor protein complex-3 cargoes. Mol. Biol. Cell, 14, 4014-4026
192. 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. Traffi c, 5, 276-283
193. Gautam, R., Chintala, S., Li, W., Zhang, Q., Tan, J., Novak, E.K., Di Pietro, S.M., Dell'Angelica, E.C., and Swank, R.T. (2004) The Hermansky-Pudlak syndrome 3 (cocoa) protein is a component of the biogenesis of lysosome-related organelles complex-2 (BLOC-2). J. Biol. Chem., 279, 12935-12942
194. Helip-Wooley, A., Westbroek, W., Dorward, H., Mommaas, M., Boissy, R.E., Gahl, W.A., and Huizing, M. (2005) Association of the Hermansky-Pudlak syndrome type-3 protein with clathrin. BMC Cell Biol., 6, 33
195. Boissy, R.E., Richmond, B., Huizing, M., Helip-Wooley, A., Zhao, Y., Koshoffer, A., and Gahl, W.A. (2005) Melanocyte-specifi c proteins are aberrantly traffi cked in melanocytes of Hermansky-Pudlak syndrome-type 3. Am. J. Pathol., 166, 231-240
196. Richmond, B., Huizing, M., Knapp, J., Koshoffer, A., Zhao, Y., Gahl, W.A., and Boissy, R.E. (2005) Melanocytes derived from patients with Hermansky-Pudlak syndrome types 1, 2, and 3 have distinct defects in cargo traffi cking. J. Invest. Dermatol., 124, 420-427
197. Helip-Wooley, A., Westbroek, W., Dorward, H.M., Koshoffer, A., Huizing, M., Boissy, R.E., and Gahl, W.A. (2007) Improper traffi cking of melanocyte -specifi c proteins in Hermansky-Pudlak syndrome type-5. J. Invest. Dermatol., 127, 1471-1478
198. Huizing, M., Pederson, B., Hess, R.A., Griffi n, A., Helip-Wooley, A., Westbroek, W., Dorward, H., O'Brien, K.J., Golas, G., Tsilou, E., et al. (2009) Clinical and cellular characterisation of Hermansky-Pudlak syndrome type 6. J. Med. Genet., 46, 803-810
199. Chiang, P.-W., Oiso, N., Gautam, R., Swank, R.T., and Spritz, R.A. (2003) The Hermansky-Pudlak syndrome 1 (HPS1) and HPS4 proteins are components of two complexes, BLOC-3 and BLOC-4, involved in the biogenesis of lysosome -related organelles. J. Biol. Chem., 278, 20332-20337
200. Kloer, D.R., Rojas, R., Ivan, V., Moriyama, K., van Vlijmen, T., Murthy, N., Ghirlando, R., van der Sluijs, P., Hurley, J.H., and Bonifacino, J.S. (2010) Assembly of the biogenesis of lysosome -related organelles complex-3 (BLOC-3) and its interaction with Rab9. J. Biol. Chem., 285, 7794-7804
201. Martina, J.A., Moriyama, K., and Bonifacino, J.S. (2003) BLOC-3, a protein complex containing the Hermansky-Pudlak syndrome gene products HPS1 and HPS4. J. Biol. Chem., 278, 29376-29384
202. Nazarian, R., Falcon-Perez, J.M., and Dell'Angelica, E.C. (2003) 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
203. Gardner, J.M., Wildenberg, S.C., Keiper, N.M., Novak, E.K., Rusiniak, M.E., Swank, R.T., Puri, N., Finger, J.N., Hagiwara, N., Lehman, A.L., et al. (1997) The mouse pale ear (ep) mutation is the homologue of human Hermansky-Pudlak syndrome. Proc. Natl. Acad. Sci. USA, 94, 9238-9243
204. Nguyen, T. and Wei, M.L. (2007) Hermansky-Pudlak HPS1/pale ear gene regulates epidermal and dermal melanocyte development. J. Invest. Dermatol., 127, 421-428
205. 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., et al. (2002) Hermansky-Pudlak syndrome is caused by mutations in HPS4, the human homolog of the mouse light-ear gene. Nat. Genet., 30, 321-324
206. Horikawa, T., Araki, K., Fukai, K., Ueda, M., Ueda, T., Ito, S., and Ichihashi, M. (2000) Heterozygous HPS1 mutations in a case of Hermansky-Pudlak syndrome with giant melanosomes. Br. J. Dermatol., 143, 635-640
207. Smith, J.W., Koshoffer, A., Morris, R.E., and Boissy, R.E. (2005) Membranous complexes characteristic of melanocytes derived from patients with Hermansky-Pudlak syndrome type 1 are macroautophagosomal entities of the lysosomal compartment. Pigment Cell Res., 18, 417-426
208. Falcon-Perez, J.M., Nazarian, R., Sabatti, C., and Dell'Angelica, E.C. (2005) Distribution and dynamics of Lamp1 -containing endocytic organelles in fi broblasts defi cient in BLOC-3. J. Cell Sci., 118, 5243-5255
209. Oh, J., Liu, Z.X., Feng, G.H., Raposo, G., and Spritz, R.A. (2000) The Hermansky-Pudlak syndrome (HPS) protein is part of a high molecular weight complex involved in biogenesis of early melanosomes. Hum. Mol. Genet., 9, 375-385
210. Wu, X., Bowers, B., Rao, K., Wei, Q., and Hammer, J.A., III (1998) Visualization of melanosome dynamics within wild-type and dilute melanocytes suggests a paradigm for myosin V function in vivo. J. Cell Biol., 143, 1899-1918
211. Nakagawa, T., Setou, M., Seog, D., Ogasawara, K., Dohmae, N., Takio, K., and Hirokawa, N. (2000) A novel motor, KIF13A, transports mannose-6 -phosphate receptor to plasma membrane through direct interaction with AP-1 complex. Cell, 103, 569-581
212. Salas-Cortes, L., Ye, F., Tenza, D., Wilhelm, C., Theos, A., Louvard, D., Raposo, G., and Coudrier, E. (2005) Myosin Ib modulates the morphology and the protein transport within multi-vesicular sorting endosomes. J. Cell Sci., 118, 4823-4832
213. Bonifacino, J.S. and Glick, B.S. (2004) The mechanisms of vesicle budding and fusion. Cell, 116, 153-166
214. Wade, N., Bryant, N.J., Connolly, L.M., Simpson, R.J., Luzio, J.P., Piper, R.C., and James, D.E. (2001) Syntaxin 7 complexes with mouse Vps10p tail interactor Ib, Syntaxin 6, vesicle -associated membrane protein (VAMP)8, and VAMP7 in B16 melanoma cells. J. Biol. Chem., 276, 19820-19827
215. McBride, H.M., Rybin, V., Murph, y.C., Giner, A., Teasdale, R., and Zerial, M. (1999) Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13. Cell, 98, 377-386
216. Prekeris, R., Klumperman, J., Chen, Y.A., and Scheller, R.H. (1998) Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes. J. Cell Biol., 143, 957-971
217. Huang, L., Kuo, Y.M., and Gitschier, J. (1999) The pallid gene encodes a novel, syntaxin 13-interacting protein involved in platelet storage pool defi ciency. Nat. Genet., 23, 329-332
218. Martinez-Arca, S., Rudge, R., Vacca, M., Raposo, G., Camonis, J., Proux -Gillardeaux, V., Daviet, L., Formstecher, E., Hamburger, A., Filippini, F., et al. (2003) A dual mechanism controlling the localization and function of exocytic v-SNAREs. Proc. Natl. Acad. Sci. USA, 100, 9011-9016
219. Sato, T.K., Rehling, P., Peterson, M.R., and Emr, S.D. (2000) Class C vps protein complex regulates vacuolar SNARE pairing and is required for vesicle docking/fusion. Mol. Cell, 6, 661-671
220. Richardson, S.C., Winistorfer, S.C., Poupon, V., Luzio, J.P., and Piper, R.C. (2004) Mammalian late vacuole protein sorting orthologues participate in early endosomal fusion and interact with the cytoskeleton. Mol. Biol. Cell, 15, 1197-1210
221. Gerst, J.E. (2003) SNARE regulators: matchmakers and matchbreakers. Biochim. Biophys. Acta, 1641, 99-110
222. Shen, J., Tareste, D.C., Paumet, F., Rothman, J.E., and Melia, T.J. (2007) Selective activation of cognate SNAREpins by Sec1/Munc18 proteins. Cell, 128, 183-195
223. Suzuki, T., Oiso, N., Gautam, R., Novak, E.K., Panthier, J.J., Suprabha, P.G., Vida, T., Swank, R.T., and Spritz, R.A. (2003) The mouse organellar biogenesis mutant buff results from a mutation in Vps33a, a homologue of yeast vps33 and Drosophila carnation. Proc. Natl. Acad. Sci. USA, 21, 21
224. Nickerson, D.P., Brett, C.L., and Merz, A.J. (2009) Vps-C complexes: gatekeepers of endolysosomal traffi c. Curr. Opin. Cell Biol., 21, 543-551
225. Zerial, M. and McBride, H. (2001) Rab proteins as membrane organizers. Nat. Rev. Mol. Cell Biol., 2, 107-119
226. Zhang, Q., Zhen, L., Li, W., Novak, E.K., Collinson, L.M., Jang, E.K., Haslam, R.J., Elliott, R.W., and Swank, R.T. (2002) Cell-specifi c abnormal prenylation of Rab proteins in platelets and melanocytes of the gunmetal mouse. Br. J. Haematol., 117, 414-423
227. Wasmeier, C., Romao, M., Plowright, L., Bennett, D.C., Raposo, G., and Seabra, M.C. (2006) Rab38 and Rab32 control post-Golgi traffi cking of melanogenic enzymes. J. Cell Biol., 175, 271-281
228. Oiso, N., Riddle, S.R., Serikawa, T., Kuramoto, T., and Spritz, R.A. (2004) The rat Ruby (R) locus is Rab38: identical mutations in Fawn-hooded and Tester-Moriyama rats derived from an ancestral Long Evans rat sub-strain. Mamm. Genome, 15, 307-314
229. Loftus, S.K., Larson, D.M., Baxter, L.L., Antonellis, A., Chen, Y., Wu, X., Jiang, Y., Bittner, M., Hammer, J.A., 3rd, and Pavan, W.J. (2002) Mutation of melanosome protein RAB38 in chocolate mice. Proc. Natl. Acad. Sci. USA, 99, 4471-4476
230. Ma, J., Plesken, H., Treisman, J.E., Edelman-Novemsky, I., and Ren, M. (2004) Lightoid and Claret: a rab GTPase and its putative guanine nucleotide exchange factor in biogenesis of Drosophila eye pigment granules. Proc. Natl. Acad. Sci. USA, 101, 11652-11657
231. Detter, J.C., Zhang, Q., Mules, E.H., Novak, E.K., Mishra, V.S., Li, W., McMurtrie, E.B., Tchernev, V.T., Wallace, M.R., Seabra, M.C., et al. (2000) Rab geranylgeranyl transferase alpha mutation in the gunmetal mouse reduces Rab prenylation and platelet synthesis. Proc. Natl. Acad. Sci. USA, 97, 4144-4149
232. Rodriguez-Fernandez, I.A. and Dell'Angelica, E.C. (2009) A data-mining approach to rank candidate protein -binding partners-the case of biogenesis of lysosome-related organelles complex-1 (BLOC-1). J. Inherit. Metab. Dis., 32, 190-203
233. Hirosaki, K., Yamashita, T., Wada, I., Jin, H.Y., and Jimbow, K. (2002) Tyrosinase and tyrosinase-related protein 1 require Rab7 for their intracellular transport. J. Invest. Dermatol., 119, 475-480
234. Jordens, I., Westbroek, W., Marsman, M., Rocha, N., Mommaas, M., Huizing, M., Lambert, J., Naeyaert, J.M., and Neefjes, J. (2006) Rab7 and Rab27a control two motor protein activities involved in melanosomal transport. Pigment Cell Res., 19, 412-423
235. Rink, J., Ghigo, E., Kalaidzidis, Y., and Zerial, M. (2005) Rab conversion as a mechanism of progression from early to late endosomes. Cell, 122, 735-749
236. Groux-Degroote, S., van Dijk, S.M., Wolthoorn, J., Neumann, S., Theos, A.C., De Mazi è re, A.M., Klumperman, J., van Meer, G., and Sprong, H. (2008) Glycolipid-dependent sorting of melanosomal from lysosomal membrane proteins by lumenal determinants. T raffi c, 9, 951-963
237. Sprong, H., Degroote, S., Claessens, T., van Drunen, J., Oorschot, V., Westerink, B.H., Hirabayashi, Y., Klumperman, J., van der Sluijs, P., and van Meer, G. (2001) Glycosphingolipids are required for sorting melanosomal proteins in the Golgi complex. J. Cell Biol., 155, 369-380.