RRC ID 43312
Author Groux-Degroote S, van Dijk SM, Wolthoorn J, Neumann S, Theos AC, De Mazière AM, Klumperman J, van Meer G, Sprong H.
Title Glycolipid-dependent sorting of melanosomal from lysosomal membrane proteins by lumenal determinants.
Journal Traffic
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.
Volume 9(6)
Pages 951-63
Published 2008-6-1
DOI 10.1111/j.1600-0854.2008.00740.x
PMID 18373728
MeSH Animals Cell Line, Tumor Lysosome-Associated Membrane Glycoproteins / metabolism Lysosome-Associated Membrane Glycoproteins / physiology* Lysosome-Associated Membrane Glycoproteins / ultrastructure Melanocytes / enzymology Melanoma / ultrastructure Melanosomes / metabolism Melanosomes / physiology* Melanosomes / ultrastructure Mice Monophenol Monooxygenase / metabolism Oxidoreductases / chemistry Oxidoreductases / metabolism Protein Structure, Tertiary Protein Transport Transfection
IF 4.045
Times Cited 22
Human and Animal Cells GM95(RCB1026) MEB4(RCB1027)