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

Published inThe Journal of biological chemistry, vol. 277, no. 51, p. 49538-49544
Publication date2002-12-20
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 indentified. 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 liquid moieties.

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Citation (ISO format)
WATANABE CASTILLON, Reika et al. Sphingolipids are required for the stable membrane association of glycosylphosphatidylinositol-anchored proteins in yeast. In: The Journal of biological chemistry, 2002, vol. 277, n° 51, p. 49538–49544. doi: 10.1074/jbc.M206209200
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ISSN of the journal0021-9258
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