title: Pmel17 initiates premelanosome morphogenesis within multivesicular bodies.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Berson
authors.forename: D C
authors.initials: DC
authors.lastname: Harper
authors.forename: D
authors.initials: D
authors.lastname: Tenza
authors.forename: G
authors.initials: G
authors.lastname: Raposo
authors.forename: M S
authors.initials: MS
authors.lastname: Marks
mesh_terms: D016475:3T3 Cells; D000818:Animals; D022162:Cytoplasmic Vesicles / Q000378:metabolism / Q000502:physiology; D004220:Disulfides; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D020460:Melanosomes / Q000378:metabolism / Q000502:physiology*; D008562:Membrane Glycoproteins; D051379:Mice; D009024:Morphogenesis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D058951:gp100 Melanoma Antigen
chemical_list: D004220:Disulfides; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C548637:PMEL protein, human; C548642:Pmel protein, mouse; D011506:Proteins; D058951:gp100 Melanoma Antigen