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J Biol Chem. 2002 Dec 20;277(51):49538-44. Epub 2002 Oct 18.

Sphingolipids are required for the stable membrane association of glycosylphosphatidylinositol-anchored proteins in yeast.

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  • 1Biozentrum of the University of Basel, Klingelbergstrasse 70, Basel 4056, Switzerland.

Abstract

Ongoing sphingolipid synthesis is specifically required in vivo for the endoplasmic reticulum (ER) to Golgi transport of glycosylphosphatidylinositol (GPI)-anchored proteins. However, the sphingolipid intermediates that are required for transport nor their role(s) have been identified. Using stereoisomers of dihydrosphingosine, together with specific inhibitors and a mutant defective for sphingolipid synthesis, we now show that ceramides and/or inositol sphingolipids are indispensable for GPI-anchored protein transport. Furthermore, in the absence of sphingolipid synthesis, a significant fraction of GPI-anchored proteins is no longer associated tightly with the ER membrane. The loose membrane association is neither because of the lack of a GPI-anchor nor because of prolonged ER retention of GPI-anchored proteins. These results indicate that ceramides and/or inositol sphingolipids are required to stabilize the association of GPI-anchored proteins with membranes. They could act either by direct involvement as membrane components or as substrates for the remodeling of GPI lipid moieties.

PMID:
12393888
[PubMed - indexed for MEDLINE]
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