title: Role of Drosophila alkaline ceramidase (Dacer) in Drosophila development and longevity.
abstract: Ceramidases catalyze the hydrolysis of ceramides to generate sphingosine (SPH) and fatty acids, and ceramide metabolism is implicated in various biological responses in Drosophila melanogaster. Here we report the cloning, biochemical characterization, and functional analysis of a Drosophila alkaline ceramidase (Dacer). Dacer, a membrane-bound protein of 284 amino acids, shares homology with yeast and mammalian alkaline ceramidases. Overexpression of Dacer in High Five insect cells increases ceramidase activity in the alkaline pH range, indicating that Dacer is a bona fide alkaline ceramidase. Dacer mRNA is highly expressed in the midgut and at the pupal stage. An inactivation of Dacer by insertional mutagenesis increases the levels of ceramides in both Drosophila pupae and adult flies. Dacer inactivation increases Drosophila pre-adult development time, lifespan, and anti-oxidative stress capacity. Collectively, these results suggest that Dacer plays an important role in the Drosophila development and longevity by controlling the metabolism of ceramides.
authors.affiliation: State Key Laboratory of Rice Biology, Key Laboratory of Molecular Biology of Crop Pathogens and Insects, the Ministry of Agriculture of China, Hangzhou, Zhejiang 310029, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.forename: Zhong-Jun
authors.initials: ZJ
authors.lastname: Gong
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Jing-Qun
authors.initials: JQ
authors.lastname: Yuan
authors.forename: Jiaan
authors.initials: J
authors.lastname: Cheng
authors.forename: Lin
authors.initials: L
authors.lastname: Tian
authors.forename: Sheng
authors.initials: S
authors.lastname: Li
authors.forename: Xin-Da
authors.initials: XD
authors.lastname: Lin
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Xu
authors.forename: Zeng-Rong
authors.initials: ZR
authors.lastname: Zhu
authors.forename: Cungui
authors.initials: C
authors.lastname: Mao
mesh_terms: D055574:Alkaline Ceramidase / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000254:growth & development* / Q000502:physiology; D005260:Female; D006801:Humans; D008136:Longevity / Q000502:physiology*; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D018384:Oxidative Stress; D011679:Pupa / Q000033:anatomy & histology / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D021241:Spectrometry, Mass, Electrospray Ionization; D013110:Sphingosine / Q000378:metabolism
chemical_list: D002518:Ceramides; D029721:Drosophila Proteins; D017382:Reactive Oxygen Species; D008780:Methyltransferases; C530958:juvenile hormone acid O-methyltransferase, Drosophila; D055574:Alkaline Ceramidase; C549190:bwa protein, Drosophila; D013110:Sphingosine