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Vol. 12, Issue 11, 3417-3427, November 2001
§ and
*Max-Planck-Institut for Biochemistry, D-82152 Martinsried,
Germany; and Lag1p and Lac1p are two homologous transmembrane proteins of the
endoplasmic reticulum in Saccharomyces cerevisiae.
Homologous genes have been found in a wide variety of eukaryotes. In
yeast, both genes, LAC1 and LAG1, are
required for efficient endoplasmic reticulum-to-Golgi transport of
glycosylphosphatidylinositol-anchored proteins. In this study,
we show that lag1Biozentrum of the University of Basel,
CH-4056 Basel, Switzerland
lac1 cells have
reduced sphingolipid levels due to a block of the fumonisin
B1-sensitive and acyl-CoA-dependent ceramide synthase reaction. The
sphingolipid synthesis defect in
lag1lac1 cells can be partially
corrected by overexpression of YPC1 or
YDC1, encoding ceramidases that have been reported to
have acyl-CoA-independent ceramide synthesis activity. Quadruple
mutant cells
(lag1lac1ypc1ydc1)
do not make any sphingolipids, but are still viable probably because they produce novel lipids. Moreover,
lag1lac1 cells are resistant to
aureobasidin A, an inhibitor of the inositolphosphorylceramide synthase, suggesting that aureobasidin A may be toxic because it leads
to increased ceramide levels. Based on these data, LAG1 and LAC1 are the first genes to be identified that are
required for the fumonisin B1-sensitive and acyl-CoA-dependent
ceramide synthase reaction.
These authors contribute equally to the work.
§
Corresponding author. E-mail address:
Howard.Riezman{at}unibas.ch.
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