Glycosphingolipids are required for sorting melanosomal proteins in the Golgi complex

Autor: Sprong, H., Degroote, S., Claessens, T., van Drunen, J., Oorschot, V.M.J., Westerink, B.H., Hirabayashi, Y., Klumperman, J., van der Sluijs, P., van Meer, G., Membraan enzymologie, Membrane Enzymology, Universiteit Utrecht, Dep Scheikunde
Přispěvatelé: Faculteit der Geneeskunde, Membraan enzymologie, Membrane Enzymology, Universiteit Utrecht, Dep Scheikunde, Groningen Research Institute of Pharmacy, Biomonitoring and Sensoring
Jazyk: angličtina
Rok vydání: 2001
Předmět:
Tyrosinase
Golgi Apparatus
melanosome
medicine.disease_cause
CYTOPLASMIC TAIL
Cell membrane
Levodopa
Mice
Sphingosine
MDCK CELLS
Cricetinae
Protein targeting
Tumor Cells
Cultured
Melanosomes
Membrane Glycoproteins
glycosphingolipid
Monophenol Monooxygenase
Pigmentation
EPITHELIAL-CELLS
Cell biology
Transport protein
Neoplasm Proteins
Protein Transport
medicine.anatomical_structure
Biochemistry
Glucosyltransferases
International
MOUSE MELANOMA-CELLS
symbols
Oxidoreductases
Endosome
protein sorting
TYROSINASE-RELATED PROTEIN-1
CHO Cells
Biology
tyrosinase
Glycosphingolipids
Article
symbols.namesake
medicine
Animals
Melanosome
Melanins
DI-LEUCINE
Binding Sites
AP-3 ADAPTER
Cell Membrane
Psychosine
Proteins
Cell Biology
Membrane transport
Golgi apparatus
TRANSPORT
Enzyme Activation
Vacuoles
TRP-1
CERAMIDE GALACTOSYLTRANSFERASE
MEMBRANE RAFTS
Cattle
Lysosomes
Zdroj: Journal of Cell Biology, 155(3), 369. Rockefeller University Press
Scopus-Elsevier
The Journal of Cell Biology
Journal of Cell Biology, 155(3), 369-379. Rockefeller University Press
Journal of Cell Biology, 155(3), 369-379. ROCKEFELLER UNIV PRESS
ISSN: 0021-9525
DOI: 10.1083/jcb.200106104
Popis: A;lthough glycosphingolipids are ubiquitously expressed and essential for multicellular organisms, surprisingly little is known about their intracellular functions. To explore the role of glycosphingolipids in membrane transport, we used the glycosphingolipid-deficient GM95 mouse melanoma cell line. We found that GM95 cells do not make melanin pigment because tyrosinase, the first and rate-limiting enzyme in melanin synthesis, was not targeted to melanosomes but accumulated in the Golgi complex. However, tyrosinase-related protein 1 still reached melanosomal structures via the plasma membrane instead of the direct pathway from the Golgi. Delivery of lysosomal enzymes from the Golgi complex to endosomes was normal, suggesting that this pathway is not affected by the absence of glycosphingolipids. Loss of pigmentation was due to tyrosinase mislocalization, since transfection of tyrosinase with an extended transmembrane domain, which bypassed the transport block, restored pigmentation. Transfection of ceramide glucosyltransferase or addition of glucosylsphingosine restored tyrosinase transport and pigmentation. We conclude that protein transport from Golgi to melanosomes via the direct pathway requires glycosphingolipids.
Databáze: OpenAIRE
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