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
|
PII |
TRA740
|
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
|
WOS Category
|
CELL BIOLOGY
|
Resource |
Human and Animal Cells |
GM95(RCB1026)
MEB4(RCB1027) |