C13C4.5/Spinster, an evolutionarily conserved protein that regulates fertility in C-elegans through a lysosome-mediated lipid metabolism process
C13C4.5/Spinster, an evolutionarily conserved protein that regulates fertility in C-elegans through a lysosome-mediated lipid metabolism process
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C13C4.5/Spinster，一种进化上保守的蛋白质，通过溶酶体介导的脂质代谢过程调节线虫的生育力
DOI：
10.1007/s13238-013-3015-z
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发表时间：
2013-05-01
期刊：
影响因子：
21.1
通讯作者：
Xu, Pingyong
中科院分区：
文献类型：
--
作者：
Han, Mei;Chang, Hao;Xu, Pingyong
几乎所有物种的脂滴都是保守的，是用于储存中性脂质的细胞质细胞器。确定脂滴调节剂将有助于解决肥胖和其他脂肪相关疾病。在本文中，我们选择了11个候选人，可能与脂质代谢的秀丽隐杆线虫。使用基于BODIPY 493/503的流式细胞术筛选，鉴定了脂肪含量的6种阴性调节剂和3种阳性调节剂。我们选择了一种脂质含量的负调控因子C13C4.5作为进一步的研究对象。C13C4.5主要表达于肠道。我们发现该基因对于维持脂滴的代谢是重要的。生化结果显示，在C13C4.5基因敲除的蠕虫中，三酰甘油（TAG）丢失了50%。受激拉曼散射（SRS）信号在C13 C4.5突变体显示，只有49.6%的脂肪含量在近端肠区和86.3%，在远端肠区相比，野生型动物。发现C13C4.5基因敲除动物的脂滴大小和强度的平均值与野生型蠕虫相比显著降低。在C13C4.5突变动物中，蠕虫肠中的LMP-1标记的膜结构也增大。最后，在C13C4.5（ok 2087）突变体中发现了育性缺陷。综上所述，这些结果表明C13 C4.5可能调节C.通过干扰溶酶体形态和功能来改变脂滴的大小和脂肪含量，从而对秀丽隐杆线虫产生影响。
Lipid droplets, which are conserved across almost all species, are cytoplasmic organelles used to store neutral lipids. Identification of lipid droplet regulators will be conducive to resolving obesity and other fat-associated diseases. In this paper, we selected 11 candidates that might be associated with lipid metabolism in Caenorhabditis elegans. Using a BODIPY 493/503-based flow cytometry screen, 6 negative and 3 positive regulators of fat content were identified. We selected one negative regulator of lipid content, C13C4.5, for future study. C13C4.5 was mainly expressed in the worm intestine. We found that this gene was important for maintaining the metabolism of lipid droplets. Biochemical results revealed that 50% of triacylglycerol (TAG) was lost in C13C4.5 knockout worms. Stimulated Raman scattering (SRS) signals in C13C4.5 mutants showed only 49.6% of the fat content in the proximal intestinal region and 86.3% in the distal intestinal region compared with wild type animals. The mean values of lipid droplet size and intensity in C13C4.5 knockout animals were found to be significantly decreased compared with those in wild type worms. The LMP-1-labeled membrane structures in worm intestines were also enlarged in C13C4.5 mutant animals. Finally, fertility defects were found in C13C4.5(ok2087) mutants. Taken together, these results indicate that C13C4.5 may regulate the fertility of C. elegans by changing the size and fat content of lipid droplets by interfering with lysosomal morphology and function.