Glycolipid-dependent sorting of melanosomal from lysosomal membrane proteins by lumenal determinants
article
Melanosomes are lysosome-related organelles that coexist with lysosomes in mammalian pigment cells. Melanosomal and lysosomal membrane proteins share similar sorting signals in their cytoplasmic tail, raising the question how they are segregated. We show that in control melanocytes, the melanosomal enzymes tyrosinase-related protein 1 (Tyrp1) and tyrosinase follow an intracellular Golgi to melanosome pathway, whereas in the absence of glycosphingolipids, they are observed to pass over the cell surface. Unexpectedly, the lysosome-associated membrane protein 1 (LAMP-1) and 2 behaved exactly opposite: they were found to travel through the cell surface in control melanocytes but followed an intracellular pathway in the absence of glycosphingolipids. Chimeric proteins having the cytoplasmic tail of Tyrp1 or tyrosinase were transported like lysosomal proteins, whereas a LAMP-1 construct containing the lumenal domain of Tyrp1 localized to melanosomes. In conclusion, the lumenal domain contains sorting information that guides Tyrp1 and probably tyrosinase to melanosomes by an intracellular route that excludes lysosomal proteins and requires glucosylceramide. © 2008 The Authors Journal compilation © 2008 Blackwell Publishing Ltd.
Topics
Adaptor complexGlycosphingolipidsLysosomal proteinMelanosomal enzymeMelanosome assemblyProtein sortingSecretory lysosomechimeric proteinglucosylceramideglycolipidglycosphingolipidlysosome associated membrane protein 1lysosome associated membrane protein 2membrane proteinmonophenol monooxygenasetranscription factortranscription factor ap 3tyrosinase related protein 1articlebiogenesiscell surfacecellular distributioncontrolled studyGolgi complexhumanhuman cellintracellular transportlysosomemelanocytemelanosomepriority journalprotein localizationprotein targetingprotein transportAnimalsCell Line, TumorLysosome-Associated Membrane GlycoproteinsMelanocytesMelanomaMelanosomesMiceMonophenol MonooxygenaseOxidoreductasesProtein Structure, TertiaryProtein TransportTransfection
TNO Identifier
240844
ISSN
13989219
Source
Traffic, 9(6), pp. 951-963.
Pages
951-963
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