Biosynthesis of mannosylinositolphosphoceramide in Saccharomyces cerevisiae is dependent on genes controlling the flow of secretory vesicles from the endoplasmic reticulum to the Golgi

Abstract

Saccharomyces cerevisiae contains several abundant phosphoinositol-containing sphingolipids, namely inositolphosphoceramides (IPCs), mannosyl-inositolphosphoceramide (MIPC), which is substituted on the headgroup with an additional mannose, and M(IP)2C, a ceramide substituted with one mannose and two phosphoinositol groups. Using well-defined temperature-sensitive secretion mutants we demonstrate that the biosynthesis of MIPC, M(IP)2C, and a subclass if IPCs is dependent on genes that are required for the vesicular transport of proteins from the ER to the Golgi. Synthesis of these lipids in intact cells is dependent on metabolic energy. A likely but tentative interpretation of the data is that the biosynthesis of these sphingolipids is restricted to the Golgi apparatus, and that one or more substrates for the biosynthesis of these sphingolipids (phosphatidylinositol, IPCs, or MIPC) are delivered to the Golgi apparatus by an obligatory vesicular transport step. Alternative models to explain the data are also discussed.