Glycolipid-dependent sorting of melanosomal from lysosomal membrane proteins by lumenal determinants.
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.
Groux-Degroote
Sophie
S
Membrane Enzymology, Bijvoet Center and Institute of Biomembranes, Utrecht University, 3584CH Utrecht, The Netherlands.
van Dijk
Suzanne M
SM
Wolthoorn
Jasja
J
Neumann
Sylvia
S
Theos
Alexander C
AC
De Mazière
Ann M
AM
Klumperman
Judith
J
van Meer
Gerrit
G
Sprong
Hein
H
D000818:Animals; D045744:Cell Line, Tumor; D051907:Lysosomal Membrane Proteins / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D008544:Melanocytes / Q000201:enzymology; D008545:Melanoma / Q000648:ultrastructure; D020460:Melanosomes / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D014162:Transfection
D051907:Lysosomal Membrane Proteins; D010088:Oxidoreductases; C064056:tyrosinase-related protein-1; D014442:Monophenol Monooxygenase