The cholesterol trafficking protein NPC1 is required for Drosophila spermatogenesis |
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Authors: | Wang Chao Ma Zhiguo Scott Matthew P Huang Xun |
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Institution: | aKey Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China;bGraduate School of Chinese Academy of Sciences, Beijing 100049, China;cDepartment of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305-5439, USA;dDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305-5439, USA;eDepartment of Bioengineering, Stanford University School of Medicine, Stanford, CA 94305-5439, USA |
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Abstract: | Niemann–Pick C (NPC) disease is a lethal neurodegenerative disorder affecting cellular sterol trafficking. Besides neurodegeneration, NPC patients also exhibit other pleiotropic conditions, indicating that NPC protein is required for other physiological processes. Previous studies indicated that a sterol shortage that in turn leads to a shortage of steroid hormones (for example, ecdysone in Drosophila) is likely to be the cause of NPC disease pathology. We have shown that mutations in Drosophila npc1, one of the two NPC disease-related genes, leads to larval lethal and male infertility. Here, we reported that npc1 mutants are defective in spermatogenesis and in particular in the membrane-remodeling individualization process. Interestingly, we found that ecdysone, the steroid hormone responsible for the larval lethal phenotype in npc1 mutants, is not required for individualization. However, supplying 7-dehydrocholesterol can partially rescue the male infertility of npc1 mutants, suggesting that a sterol shortage is responsible for the spermatogenesis defects. In addition, the individualization defects of npc1 mutants were enhanced at high temperature, suggesting that the sterol shortage may lead to temperature-sensitive defects in the membrane-remodeling process. Together, our study reveals a sterol-dependent, ecdysone-independent mechanism of NPC1 function in Drosophila spermatogenesis. |
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Keywords: | NPC1 Spermatogenesis Individualization Drosophila Sterols |
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