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Title: The protein kinase Sch9 is a key regulator of sphingolipid metabolism in Saccharomyces cerevisiae
Authors: Swinnen, Erwin *
Wilms, Tobias *
Idkowiak-Baldys, Jolanta
Smets, Bart
De Snijder, Pepijn
Accardo, Sabina
Ghillebert, Ruben
Thevissen, Karin
Cammue, Bruno
De Vos, Dirk
Bielawski, Jacek
Hannun, Yusuf A
Winderickx, Joris # ×
Issue Date: 25-Jan-2014
Publisher: American Society for Cell Biology
Series Title: Molecular Biology of the Cell vol:1 pages:196-211
Abstract: The Saccharomyces cerevisiae protein kinase Sch9 has been demonstrated to be an in vitro and in vivo effector of sphingolipid signaling. In this study, the link between Sch9 and sphingolipid metabolism in S. cerevisiae was examined in vivo based on the observation that the sch9Δ mutant displays altered sensitivities to various inhibitors of sphingolipid metabolism, i.e. myriocin and aureobasidin A. Sphingolipid profiling indicated that sch9Δ cells have increased levels of long-chain bases and long-chain base-1 phosphates, decreased levels of several species of (phyto)ceramides, and altered ratios of complex sphingolipids. We show that the TORC1 - Sch9 signaling pathway functions to repress the expression of the ceramidase genes YDC1 and YPC1, thereby unveiling, for the first time in yeast, a nutrient-dependent transcriptional mechanism involved in the regulation of sphingolipid metabolism. Additionally, we established that Sch9 affects the activity of the inositol phosphosphingolipid phospholipase C, Isc1, which is required for ceramide production by hydrolysis of complex sphingolipids. As sphingolipid metabolites play a crucial role in the regulation of stress tolerance and longevity of yeast cells, our data provide a model in which Sch9 regulates the latter phenotypes by acting not only as an effector but also as a regulator of sphingolipid metabolism.
ISSN: 1059-1524
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Centre for Surface Chemistry and Catalysis
Division of Bioeconomics
Molecular Physiology of Plants and Micro-organisms Section - miscellaneous
Centre of Microbial and Plant Genetics
* (joint) first author
× corresponding author
# (joint) last author

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