The cholesterol trafficking protein NPC1 is required for Drosophila spermatogenesis
The cholesterol trafficking protein NPC1 is required for Drosophila spermatogenesis
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果蝇精子发生需要胆固醇运输蛋白 NPC1
DOI：
10.1016/j.ydbio.2010.12.042
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发表时间：
2011-03-01
影响因子：
2.7
通讯作者：
Huang, Xun
中科院分区：
文献类型：
--
作者：
Wang, Chao;Ma, Zhiguo;Huang, Xun
Niemann-Pick C(NPC)病是一种影响细胞类固醇转运的致死性神经退行性疾病。除了神经退行性变，鼻咽癌患者还表现出其他多效性情况，这表明鼻咽癌蛋白是其他生理过程所必需的。先前的研究表明，类固醇缺乏进而导致类固醇激素(如果蝇中的蜕皮激素)的缺乏可能是鼻咽癌疾病病理的原因。我们已经证明，果蝇NPC1基因的突变会导致幼虫致死和男性不育。在这里，我们报告了NPC1突变体在精子发生中的缺陷，特别是在膜重塑个性化过程中。有趣的是，我们发现蜕皮激素，在NPC1突变体中导致幼虫致命表型的类固醇激素，不是个性化所必需的。然而，补充7-脱氢胆固醇可以部分挽救NPC1突变体的男性不育，这表明类固醇短缺是导致精子发生缺陷的原因。此外，NPC1突变体的个体化缺陷在高温下增强，提示甾醇短缺可能导致膜重塑过程中的温度敏感性缺陷。综上所述，我们的研究揭示了NPC1在果蝇精子发生中的作用机制，该机制依赖于固醇，不依赖于蜕皮激素。(C)2011 Elsevier Inc.保留所有权利。
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. (C) 2011 Elsevier Inc. All rights reserved.