Title
Glycolipid-dependent sorting of melanosomal from lysosomal membrane proteins by lumenal determinants
Author
Groux-Degroote, S.
van Dijk, S.M.
Wolthoorn, J.
Neumann, S.
Theos, A.C.
de Mazière, A.M.
Klumperman, J.
van Meer, G.
Sprong, H.
TNO Kwaliteit van Leven
Publication year
2008
Abstract
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.
Subject
Biology
Adaptor complex
Glycosphingolipids
Lysosomal protein
Melanosomal enzyme
Melanosome assembly
Protein sorting
Secretory lysosome
chimeric protein
glucosylceramide
glycolipid
glycosphingolipid
lysosome associated membrane protein 1
lysosome associated membrane protein 2
membrane protein
monophenol monooxygenase
transcription factor
transcription factor ap 3
tyrosinase related protein 1
article
biogenesis
cell surface
cellular distribution
controlled study
Golgi complex
human
human cell
intracellular transport
lysosome
melanocyte
melanosome
priority journal
protein localization
protein targeting
protein transport
Animals
Cell Line, Tumor
Lysosome-Associated Membrane Glycoproteins
Melanocytes
Melanoma
Melanosomes
Mice
Monophenol Monooxygenase
Oxidoreductases
Protein Structure, Tertiary
Protein Transport
Transfection
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DOI
https://doi.org/10.1111/j.1600-0854.2008.00740.x
TNO identifier
240844
ISSN
1398-9219
Source
Traffic, 9 (6), 951-963
Document type
article