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Role of Drosophila alkaline ceramidase (Dacer) in Drosophila development and longevity |
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| Authors: | Qiong Yang Zhong-Jun Gong Ying Zhou Jing-Qun Yuan Jiaan Cheng Lin Tian Sheng Li Xin-Da Lin Ruijuan Xu Zeng-Rong Zhu Cungui Mao |
| Institution: | 1. 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 2. The Institute of Insect Sciences, Zhejiang University, Hangzhou, Zhejiang, 310029, China 8. Institute of Plant Protection, Jiangsu Academy of Agricultural Sciences, Nanjing, Jiangsu, 210014, China 3. Center for Chemical Analysis and Detection, Zhejiang University, Hangzhou, Zhejiang, 310029, China 4. Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200032, China 5. College of Life Sciences, China Jiliang University, Hangzhou, Zhejiang, 310018, China 6. Department of Medicine and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA 7. Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC, 29425, USA |
| 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. |
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