title: Rab7 is a critical mediator in vesicular transport of tyrosinase-related protein 1 in melanocytes.
abstract: How melanosomal proteins such as enzymic proteins (tyrosinase and tyrosinase-related proteins, Tyrps) and structural protein (gp100) are transported from Golgi to melanosomal compartments is not yet fully understood. A number of small GTPases have been found to be associated with melanosomes and we have identified one of them, Rab7, a regulator of vesicular transport, organelle motility, phospholipid signaling and cytosolic degradative machinery, as being involved in the transport of Tyrp1 from Golgi to stage I melanosomes. This study further characterizes the role of Rab7 as a regulator of differential sorting of melanosomal proteins in this process. Murine melanocytes were transiently transfected with a plasmid encoding either wild-type (Rab7WT), constitutively active (Rab7Q67L) or dominant-negative (Rab7N125I and Rab7T22N) Rab7. Through immunocytostaining and confocal laser scanning microscopy, we quantitatively compared the bio-distribution of melanosomal proteins between Rab7WT-expressing cells and mutant Rab7-expressing cells. We also characterized their differential elimination from melanosomal compartments by Rab7 by utilizing a proteasome inhibitor, MG132. Our findings indicate that Rab7 plays an important role in differential sorting of tyrosinase, Tyrp1 and gp100 in early melanogenesis cascade, and that it is more specifically involved with Tyrp1 than tyrosinase and gp100 in the trafficking from Golgi to melanosomes and the specific exit from the degradative process.
authors.affiliation: Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tokimasa
authors.initials: T
authors.lastname: Hida
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sohma
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kokai
authors.forename: Akinori
authors.initials: A
authors.lastname: Kawakami
authors.forename: Kuninori
authors.initials: K
authors.lastname: Hirosaki
authors.forename: Masae
authors.initials: M
authors.lastname: Okura
authors.forename: Noriko
authors.initials: N
authors.lastname: Tosa
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamashita
authors.forename: Kowichi
authors.initials: K
authors.lastname: Jimbow
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006056:Golgi Apparatus / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000378:metabolism*; D020460:Melanosomes / Q000378:metabolism; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D021381:Protein Transport; D014162:Transfection; D058951:gp100 Melanoma Antigen / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D000090802:rab7 GTP-Binding Proteins
chemical_list: D008543:Melanins; D058951:gp100 Melanoma Antigen; D000090802:rab7 GTP-Binding Proteins; C000716465:rab7 GTP-binding proteins, mouse; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase; D020691:rab GTP-Binding Proteins