C13C4.5/Spinster, an evolutionarily conserved protein that regulates fertility in C. elegans through a lysosome-mediated lipid metabolism process  

作　　者：Mei Han Hao Chang Peng Zhang Tao Chen Yanhua Zhao Yongdeng Zhang Pingsheng Liu Tao Xu Pingyong Xu 

机构地区：[1]National Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]School of Life Sciences,University of Science and Technology of China,Hefei 230027,China [4]College of Engineering,and Biodynamic Optical Imaging Center(BIOPIC),Peking University,Beijing 100871,China [5]Key Laboratory of Interdisciplinary Research,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China

出　　处：《Protein & Cell》2013年第5期364-372,共9页蛋白质与细胞（英文版）

基　　金：support from the National Basic Research Program(973 Program)(Nos.2013CB910103 and 2010CB912303);the National Natural Science Foundation of China(Grant Nos.31170818 and 31270910);the project from the Chinese Academy of Sciences(KSCX2-EW-Q-11).

摘　　要：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.

关 键 词：C13C4.5 Spinster lipid droplet SRS mi-croscopy lysosomal enlargement FERTILITY 

分 类 号：R57[医药卫生—消化系统]