title: CDase is a pan-ceramidase in Drosophila.
abstract: Ceramidases catalyze the conversion of ceramide to sphingosine. They are acylaminohydrolases that catalyze the deacylation of the amide-linked saturated fatty acid from ceramide to generate sphingosine. They also catalyze the reverse reaction of ceramide biosynthesis using sphingosine and fatty acid. In mammals, different proteins catalyze these reactions while individually exhibiting optimal activity over a narrow pH range and have been accordingly called acid, neutral, and alkaline ceramidases. Several genes encode for variants of alkaline ceramidase in mammals. Brainwashing (Bwa) is the only putative alkaline ceramidase homologue present in Drosophila. In this study we have demonstrated that BWA does not exhibit ceramidase activity and that bwa null mutants display no loss of ceramidase activity. Instead, the neutral ceramidase gene CDase encodes the protein that is responsible for all measurable ceramidase activity in Drosophila. Our studies show strong genetic interaction of Bwa with CDase and the Drosophila ceramide kinase gene (DCERK). We show that, although BWA is unlikely to be a ceramidase, it is a regulator of sphingolipid flux in Drosophila. Bwa exhibits strong genetic interaction with other genes coding for ceramide-metabolizing enzymes. This interaction might partly explain its original identification as a ceramidase.
authors.affiliation: Laboratory of Cell And Developmental Signaling, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Changqing
authors.initials: C
authors.lastname: Yuan
authors.forename: Raghavendra Pralhada
authors.initials: RP
authors.lastname: Rao
authors.forename: Nahid
authors.initials: N
authors.lastname: Jesmin
authors.forename: Takeshi
authors.initials: T
authors.lastname: Bamba
authors.forename: Kunio
authors.initials: K
authors.lastname: Nagashima
authors.forename: Alberto
authors.initials: A
authors.lastname: Pascual
authors.forename: Thomas
authors.initials: T
authors.lastname: Preat
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Fukusaki
authors.forename: Usha
authors.initials: U
authors.lastname: Acharya
authors.forename: Jairaj K
authors.initials: JK
authors.lastname: Acharya
mesh_terms: D000818:Animals; D055572:Ceramidases / Q000235:genetics / Q000378:metabolism*; D002518:Ceramides / Q000378:metabolism*; D004330:Drosophila / Q000201:enzymology* / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D013058:Mass Spectrometry; D017384:Sequence Deletion; D013107:Sphingolipids / Q000235:genetics / Q000378:metabolism*; D013110:Sphingosine / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D002518:Ceramides; D029721:Drosophila Proteins; D013107:Sphingolipids; D055572:Ceramidases; D013110:Sphingosine