Rab7 regulates maturation of melanosomal matrix protein gp100/Pmel17/Silv.
Melanosome biogenesis consists of multistep processes that involve synthesis of melanosomal protein, which is followed by vesicle transport/fusion and post-translational modifications such as glycosylation, proteolysis, and oligomerization. Because of its complexity, the details of the molecular mechanism of melanosome biogenesis are not yet fully understood. Here, we report that, in MMAc melanoma cells, wild-type (WT) Rab7 and its dominant-active mutant (Rab7-Q67L), but not its dominant-negative mutant (Rab7-T22N), were colocalized in the perinuclear region with granules containing Stage I melanosomes, where the full-length, immature gp100/Pmel17/Silv was present. It was also found that overexpression of Rab7-Q67L and, to a lesser extent, Rab7-WT increased the amount of proteolytically processed, mature gp100. However, Rab7-T22N did not show such an effect. Moreover, siRNA-mediated Rab7 knockdown considerably inhibited gp100 maturation. These results collectively suggest that the GTP-bound form of Rab7 promotes melanogenesis through the regulation of gp100 maturation in melanoma cells.
Kawakami
Akinori
A
Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Sakane
Fumio
F
Imai
Shin-ichi
S
Yasuda
Satoshi
S
Kai
Masahiro
M
Kanoh
Hideo
H
Jin
Hai-Ying
HY
Hirosaki
Kuninori
K
Yamashita
Toshiharu
T
Fisher
David E
DE
Jimbow
Kowichi
K
D002478:Cells, Cultured; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins / Q000032:analysis; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D020460:Melanosomes / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D058951:gp100 Melanoma Antigen; D020691:rab GTP-Binding Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D000090802:rab7 GTP-Binding Proteins
C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; C548637:PMEL protein, human; D034741:RNA, Small Interfering; D058951:gp100 Melanoma Antigen; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D010088:Oxidoreductases; C489799:TYRP1 protein, human; D014442:Monophenol Monooxygenase; D020691:rab GTP-Binding Proteins