Ceramide synthesis enhances transport of GPI-anchored proteins to the Golgi apparatus in yeast.
Inhibition of ceramide synthesis by a fungal metabolite, myriocin, leads to a rapid and specific reduction in the rate of transport of glycosylphosphatidylinositol (GPI)-anchored proteins to the Golgi apparatus without affecting transport of soluble or transmembrane proteins. Inhibition of ceramide biosynthesis also quickly blocks remodelling of GPI anchors to their ceramide-containing, mild base-resistant forms. These results suggest that the pool of ceramide is rapidly depleted from early points of the secretory pathway and that its presence at these locations enhances transport of GPI-anchored proteins specifically. A mutant that is resistant to myriocin reverses its effect on GPI-anchored protein transport without reversing its effects on ceramide synthesis and remodelling. Two hypotheses are proposed to explain the role of ceramide in the transport of GPI-anchored proteins.
Horvath
A
A
Biozentrum University of Basel, Switzerland.
Sütterlin
C
C
Manning-Krieg
U
U
Movva
N R
NR
Riezman
H
H
D000217:Acyltransferases / Q000037:antagonists & inhibitors; D000935:Antifungal Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002518:Ceramides / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D005656:Fungal Proteins / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D051102:Serine C-Palmitoyltransferase; D013107:Sphingolipids / Q000378:metabolism
D000935:Antifungal Agents; D002518:Ceramides; D005229:Fatty Acids, Monounsaturated; D005656:Fungal Proteins; C066709:GAS1 protein, S cerevisiae; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D000217:Acyltransferases; D051102:Serine C-Palmitoyltransferase; C001996:thermozymocidin