Sply regulation of sphingolipid signaling molecules is essential for Drosophila development.
Sphingosine-1-phosphate is a sphingolipid metabolite that regulates cell proliferation, migration and apoptosis through specific signaling pathways. Sphingosine-1-phosphate lyase catalyzes the conversion of sphingosine-1-phosphate to ethanolamine phosphate and a fatty aldehyde. We report the cloning of the Drosophila sphingosine-1-phosphate lyase gene (Sply) and demonstrate its importance for adult muscle development and integrity, reproduction and larval viability. Sply expression is temporally regulated, with onset of expression during mid-embryogenesis. Sply null mutants accumulate both phosphorylated and unphosphorylated sphingoid bases and exhibit semi-lethality, increased apoptosis in developing embryos, diminished egg-laying, and gross pattern abnormalities in dorsal longitudinal flight muscles. These defects are corrected by restoring Sply expression or by introduction of a suppressor mutation that diminishes sphingolipid synthesis and accumulation of sphingolipid intermediates. This is the first demonstration of novel and complex developmental pathologies directly linked to a disruption of sphingolipid catabolism in metazoans.
Herr
Deron R
DR
Department of Biology and Molecular Biology Institute, San Diego State University, San Diego, CA 92182-4614, USA.
Fyrst
Henrik
H
Phan
Van
V
Heinecke
Karie
K
Georges
Rana
R
Harris
Greg L
GL
Saba
Julie D
JD
D000446:Aldehyde-Lyases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D005260:Female; D005298:Fertility; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D008954:Models, Biological; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000254:growth & development; D016254:Mutagenesis, Insertional; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism*
D029721:Drosophila Proteins; D013107:Sphingolipids; D004247:DNA; D000446:Aldehyde-Lyases; C000619494:Sply protein, Drosophila; C022649:sphingosine 1-phosphate lyase (aldolase)