Role of Drosophila alkaline ceramidase (Dacer) in Drosophila development and longevity.
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.
Yang
Qiong
Q
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.
Gong
Zhong-Jun
ZJ
Zhou
Ying
Y
Yuan
Jing-Qun
JQ
Cheng
Jiaan
J
Tian
Lin
L
Li
Sheng
S
Lin
Xin-Da
XD
Xu
Ruijuan
R
Zhu
Zeng-Rong
ZR
Mao
Cungui
C
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
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