title: Sply regulation of sphingolipid signaling molecules is essential for Drosophila development.
abstract: 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.
authors.affiliation: Department of Biology and Molecular Biology Institute, San Diego State University, San Diego, CA 92182-4614, USA.
authors.forename: Deron R
authors.initials: DR
authors.lastname: Herr
authors.forename: Henrik
authors.initials: H
authors.lastname: Fyrst
authors.forename: Van
authors.initials: V
authors.lastname: Phan
authors.forename: Karie
authors.initials: K
authors.lastname: Heinecke
authors.forename: Rana
authors.initials: R
authors.lastname: Georges
authors.forename: Greg L
authors.initials: GL
authors.lastname: Harris
authors.forename: Julie D
authors.initials: JD
authors.lastname: Saba
mesh_terms: 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*
chemical_list: D029721:Drosophila Proteins; D013107:Sphingolipids; D004247:DNA; D000446:Aldehyde-Lyases; C000619494:Sply protein, Drosophila; C022649:sphingosine 1-phosphate lyase (aldolase)