Opposite and redundant roles of the two Drosophila perilipins in lipid mobilization
Opposite and redundant roles of the two Drosophila perilipins in lipid mobilization
复制标题
两种果蝇周脂质在脂质动员中的相反和冗余作用
DOI：
10.1242/jcs.101329
复制
发表时间：
2012-08-01
影响因子：
4
通讯作者：
Huang, Xun
中科院分区：
文献类型：
--
作者：
Bi, Junfeng;Xiang, Yanhui;Huang, Xun
摘要脂滴是细胞中主要的脂质储存场所。脂滴稳态受脂酶的表面可及性调节。哺乳动物脂肪甘油三酯脂肪酶（ATGL）和脂肪敏感脂肪酶（HSL）分别是基础和刺激脂解的两种关键脂肪酶。脂周蛋白是最著名的脂滴表面蛋白，可以募集脂肪酶或阻止脂肪酶进入脂滴。哺乳动物有五个围脂蛋白，这往往表现出冗余的功能，排除了个别围脂蛋白在体内的确切作用的分析。果蝇只有两种perilipins，PLIN 1/LSD-1和PLIN 2/LSD-2。先前的研究表明，PLIN 2对于保护脂滴免受由Brummer（BMM）（ATGL的果蝇同源物）介导的脂解作用是重要的。在这项研究中，我们报告PLIN 1和果蝇HSL的功能分析。功能丧失和过表达研究表明，与PLIN 2不同，PLIN 1可能促进脂质动员。在饥饿条件下，HSL从胞质溶胶募集到脂滴表面，并且PLIN 1对于HSL的饥饿诱导的脂滴定位是必需的。此外，对plin 1、plin 2双突变体的表型分析显示，PLIN 1和PLIN 2可能在保护脂滴免于脂解方面具有冗余功能。因此，这两种果蝇perilipins具有相反和冗余的作用。结构域交换和缺失分析表明PLIN 1的C-末端区域赋予PLIN 1功能特异性。我们的研究强调了果蝇perilipin蛋白的复杂作用和进化保守的调节HSL易位perilipins。
Summary Lipid droplets are the main lipid storage sites in cells. Lipid droplet homeostasis is regulated by the surface accessibility of lipases. Mammalian adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are two key lipases for basal and stimulated lipolysis, respectively. Perilipins, the best known lipid droplet surface proteins, can either recruit lipases or prevent the access of lipases to lipid droplets. Mammals have five perilipin proteins, which often exhibit redundant functions, precluding the analysis of the exact role of individual perilipins in vivo. Drosophila have only two perilipins, PLIN1/LSD-1 and PLIN2/LSD-2. Previous studies revealed that PLIN2 is important for protecting lipid droplets from lipolysis mediated by Brummer (BMM), the Drosophila homolog of ATGL. In this study, we report the functional analysis of PLIN1 and Drosophila HSL. Loss-of-function and overexpression studies reveal that unlike PLIN2, PLIN1 probably facilitates lipid mobilization. HSL is recruited from the cytosol to the surface of lipid droplets under starved conditions and PLIN1 is necessary for the starved induced lipid droplet localization of HSL. Moreover, phenotypic analysis of plin1;plin2 double mutants revealed that PLIN1 and PLIN2 might have redundant functions in protecting lipid droplets from lipolysis. Therefore, the two Drosophila perilipins have both opposite and redundant roles. Domain swapping and deletion analyses indicate that the C-terminal region of PLIN1 confers functional specificity to PLIN1. Our study highlights the complex roles of Drosophila perilipin proteins and the evolutionarily conserved regulation of HSL translocation by perilipins.