Submitted on January 31, 2008
Revised on February 20, 2008
Accepted on February 22, 2008
New insights into sphingolipid metabolism and function in budding yeast
Robert C. Dickson
Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY 40526-0509
Corresponding Author: bobd{at}uky.edu
Our understanding of sphingolipid metabolism and functions in the baker’s yeast Saccharomyces cerevisiae has progressed substantially in the past two years. Yeast sphingolipids contain a C26-acyl moiety and all of the genes necessary for making these long chain fatty acids have been identified and a mechanism for how chain length is determined has been proposed. Advances in understanding how de novo synthesis of ceramide and complex sphingolipids is regulated have been made and they demonstrate that the Target Of Rapamycin Complex 2 (TORC2) controls ceramide synthase activity. Other work shows that TORC2 regulates the level of complex sphingolipids in a pathway using the Slm1 and Slm2 proteins to control the protein phosphatase calcineurin which regulates breakdown of complex sphingolipids. The activity of Slm1 and Slm2 has also been shown to be regulated during heat stress by phosphoinositides and TORC2 along with sphingoid long-chain bases (LCBs) and the Pkh1 and Pkh2 protein kinases to control the actin cytoskeleton, trafficking of nutrient transporters and cell viability. Together these results provide the first molecular insights into understanding previous genetic interaction data that indicated a connection between sphingolipids and the TORC2 and phosphoinositide signaling networks. This new knowledge provides a foundation for greatly advancing our understanding of sphingolipid biology in yeast.
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