Schlank, a member of the ceramide synthase family controls growth and body fat in Drosophila.
Ceramide synthases are highly conserved transmembrane proteins involved in the biosynthesis of sphingolipids, which are essential structural components of eukaryotic membranes and can act as second messengers regulating tissue homeostasis. However, the role of these enzymes in development is poorly understood due to the lack of animal models. We identified schlank as a new Drosophila member of the ceramide synthase family. We demonstrate that schlank is involved in the de novo synthesis of a broad range of ceramides, the key metabolites of sphingolipid biosynthesis. Unexpectedly, schlank mutants also show reduction of storage fat, which is deposited as triacylglyerols in the fat body. We found that schlank can positively regulate fatty acid synthesis by promoting the expression of sterol-responsive element-binding protein (SREBP) and SREBP-target genes. It further prevents lipolysis by downregulating the expression of triacylglycerol lipase. Our results identify schlank as a new regulator of the balance between lipogenesis and lipolysis in Drosophila. Furthermore, our studies of schlank and the mammalian Lass2 family member suggest a novel role for ceramide synthases in regulating body fat metabolism.
Bauer
Reinhard
R
LIMES-Institute, Program Unit Development, Genetics & Molecular Physiology, Laboratory for Molecular Developmental Biology, University of Bonn, Bonn, Germany. r.bauer@uni-bonn.de
Voelzmann
André
A
Breiden
Bernadette
B
Schepers
Ute
U
Farwanah
Hany
H
Hahn
Ines
I
Eckardt
Franka
F
Sandhoff
Konrad
K
Hoch
Michael
M
D000273:Adipose Tissue / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development*; D005260:Female; D007814:Larva / Q000201:enzymology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D050155:Lipogenesis / Q000502:physiology; D008066:Lipolysis / Q000502:physiology; D008297:Male; D005810:Multigene Family / Q000502:physiology*; D010088:Oxidoreductases / Q000235:genetics / Q000502:physiology*
D029721:Drosophila Proteins; D010088:Oxidoreductases; C108138:dihydroceramide desaturase