Pmel17 Initiates Premelanosome Morphogenesis Within Multivesicular Bodies

Overview

Journal Mol Biol Cell

Specialties Cell Biology
Molecular Biology

Date 2001 Nov 6

PMID 11694580

Citations 144

Authors

J F Berson

D C Harper

D Tenza

G Raposo

M S Marks

Affiliations

Soon will be listed here.

Abstract

Melanosomes are tissue-specific organelles within which melanin is synthesized and stored. The melanocyte-specific glycoprotein Pmel17 is enriched in the lumen of premelanosomes, where it associates with characteristic striations of unknown composition upon which melanin is deposited. However, Pmel17 is synthesized as an integral membrane protein. To clarify its physical linkage to premelanosomes, we analyzed the posttranslational processing of human Pmel17 in pigmented and transfected nonpigmented cells. We show that Pmel17 is cleaved in a post-Golgi compartment into two disulfide-linked subunits: a large lumenal subunit, M alpha, and an integral membrane subunit, M beta. The two subunits remain associated intracellularly, indicating that detectable M alpha remains membrane bound. We have previously shown that Pmel17 accumulates on intralumenal membrane vesicles and striations of premelanosomes in pigmented cells. In transfected nonpigmented cells Pmel17 associates with the intralumenal membrane vesicles of multivesicular bodies; cells overexpressing Pmel17 also display structures resembling premelanosomal striations within these compartments. These results suggest that Pmel17 is sufficient to drive the formation of striations from within multivesicular bodies and is thus directly involved in the biogenesis of premelanosomes.

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References

Maresh G, Wang W, Beam K, Malacko A, Hellstrom I, Hellstrom K . Differential processing and secretion of the melanoma-associated ME20 antigen. Arch Biochem Biophys. 1994; 311(1):95-102. DOI: 10.1006/abbi.1994.1213. View

Maresh G, Marken J, Neubauer M, Aruffo A, Hellstrom I, Hellstrom K . Cloning and expression of the gene for the melanoma-associated ME20 antigen. DNA Cell Biol. 1994; 13(2):87-95. DOI: 10.1089/dna.1994.13.87. View

Zhou B, Kobayashi T, Donatien P, Bennett D, Hearing V, Orlow S . Identification of a melanosomal matrix protein encoded by the murine si (silver) locus using "organelle scanning". Proc Natl Acad Sci U S A. 1994; 91(15):7076-80. PMC: 44341. DOI: 10.1073/pnas.91.15.7076. View

Adema G, de Boer A, Vogel A, Loenen W, Figdor C . Molecular characterization of the melanocyte lineage-specific antigen gp100. J Biol Chem. 1994; 269(31):20126-33. View

Kobayashi T, Urabe K, Orlow S, Higashi K, Imokawa G, Kwon B . The Pmel 17/silver locus protein. Characterization and investigation of its melanogenic function. J Biol Chem. 1994; 269(46):29198-205. View

Peters P, Raposo G, Neefjes J, Oorschot V, Leijendekker R, Geuze H . Major histocompatibility complex class II compartments in human B lymphoblastoid cells are distinct from early endosomes. J Exp Med. 1995; 182(2):325-34. PMC: 2192145. DOI: 10.1084/jem.182.2.325. View

Marks M, Roche P, van Donselaar E, Woodruff L, Peters P, Bonifacino J . A lysosomal targeting signal in the cytoplasmic tail of the beta chain directs HLA-DM to MHC class II compartments. J Cell Biol. 1995; 131(2):351-69. PMC: 2199989. DOI: 10.1083/jcb.131.2.351. View

Donatien P, Orlow S . Interaction of melanosomal proteins with melanin. Eur J Biochem. 1995; 232(1):159-64. DOI: 10.1111/j.1432-1033.1995.tb20794.x. View

Lee Z, Hou L, Moellmann G, Kuklinska E, Antol K, Fraser M . Characterization and subcellular localization of human Pmel 17/silver, a 110-kDa (pre)melanosomal membrane protein associated with 5,6,-dihydroxyindole-2-carboxylic acid (DHICA) converting activity. J Invest Dermatol. 1996; 106(4):605-10. DOI: 10.1111/1523-1747.ep12345163. View

10.

Chakraborty A, Platt J, Kim K, Kwon B, Bennett D, Pawelek J . Polymerization of 5,6-dihydroxyindole-2-carboxylic acid to melanin by the pmel 17/silver locus protein. Eur J Biochem. 1996; 236(1):180-8. DOI: 10.1111/j.1432-1033.1996.t01-1-00180.x. View

11.

Raposo G, Nijman H, Stoorvogel W, Liejendekker R, Harding C, Melief C . B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996; 183(3):1161-72. PMC: 2192324. DOI: 10.1084/jem.183.3.1161. View

12.

Liou W, Geuze H, Slot J . Improving structural integrity of cryosections for immunogold labeling. Histochem Cell Biol. 1996; 106(1):41-58. DOI: 10.1007/BF02473201. View

13.

Kikuchi A, Shimizu H, Nishikawa T . Expression and ultrastructural localization of HMB-45 antigen. Br J Dermatol. 1996; 135(3):400-5. View

14.

Swank R, NOVAK E, McGarry M, Rusiniak M, Feng L . Mouse models of Hermansky Pudlak syndrome: a review. Pigment Cell Res. 1998; 11(2):60-80. DOI: 10.1111/j.1600-0749.1998.tb00713.x. View

15.

Seiji M, Fitzpatrick T, Simpson R, BIRBECK M . Chemical composition and terminology of specialized organelles (melanosomes and melanin granules) in mammalian melanocytes. Nature. 1963; 197:1082-4. DOI: 10.1038/1971082a0. View

16.

Marks M, Woodruff L, Ohno H, Bonifacino J . Protein targeting by tyrosine- and di-leucine-based signals: evidence for distinct saturable components. J Cell Biol. 1996; 135(2):341-54. PMC: 2121048. DOI: 10.1083/jcb.135.2.341. View

17.

Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y . Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity. 2000; 12(1):71-81. DOI: 10.1016/s1074-7613(00)80160-0. View

18.

Berson J, Frank D, Calvo P, Bieler B, Marks M . A common temperature-sensitive allelic form of human tyrosinase is retained in the endoplasmic reticulum at the nonpermissive temperature. J Biol Chem. 2000; 275(16):12281-9. DOI: 10.1074/jbc.275.16.12281. View

19.

Kobayashi T, Vischer U, Rosnoblet C, Lebrand C, Lindsay M, Parton R . The tetraspanin CD63/lamp3 cycles between endocytic and secretory compartments in human endothelial cells. Mol Biol Cell. 2000; 11(5):1829-43. PMC: 14887. DOI: 10.1091/mbc.11.5.1829. View

20.

Youssefian T, Cramer E . Megakaryocyte dense granule components are sorted in multivesicular bodies. Blood. 2000; 95(12):4004-7. View