CERAMIDE SYNTHESIS ENHANCES TRANSPORT OF GPI-ANCHORED PROTEINS TO THEGOLGI-APPARATUS IN YEAST

Inhibition of ceramide synthesis by a fungal metabolite; myriocin, lea ds to a rapid and specific reduction in the rate of transport of glyco sylphosphatidylinositol (GPI)-anchored proteins to the Golgi apparatus without affecting transport of soluble or transmembrane proteins. Inh ibition of ceramide biosynthesis also quickly blocks remodelling of GP I anchors to their ceramide-containing, mild base-resistant forms. The se results suggest that the pool of ceramide is rapidly depleted from early points of the secretory pathway and that its presence at these l ocations enhances transport of GPI-anchored proteins specifically. A m utant that is resistant to myriocin reverses its effect on GPI-anchore d protein transport without reversing its effects on ceramide synthesi s and remodelling. Two hypotheses are proposed to explain the role of ceramide in the transport of GPI-anchored proteins.