State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
PLoS One. 2012;7(2):e32086. doi: 10.1371/journal.pone.0032086. Epub 2012 Feb 14.
Lipids are essential components of all organisms. Within cells, lipids are mainly stored in a specific type of organelle, called the lipid droplet. The molecular mechanisms governing the dynamics of lipid droplets have been little explored. The protein composition of lipid droplets has been analyzed in numerous proteomic studies, and a large number of lipid droplet-associated proteins have been identified, including Rab small GTPases. Rab proteins are known to participate in many intracellular membranous events; however, their exact role in lipid droplets is largely unexplored. Here we systematically investigate the roles of Drosophila Rab family proteins in lipid storage in the larval adipose tissue, fat body. Rab32 and several other Rabs were found to affect the size of lipid droplets as well as lipid levels. Further studies showed that Rab32 and Rab32 GEF/Claret may be involved in autophagy, consequently affecting lipid storage. Loss-of-function mutants of several components in the autophagy pathway result in similar effects on lipid storage. These results highlight the potential functions of Rabs in regulating lipid metabolism.
脂质是所有生物体的必需组成部分。在细胞内,脂质主要储存在一种特殊的细胞器中,称为脂滴。然而,脂质滴动力学的分子机制还很少被探索。在众多蛋白质组学研究中已经分析了脂滴的蛋白质组成,并且已经鉴定出大量与脂滴相关的蛋白质,包括 Rab 小 GTP 酶。已知 Rab 蛋白参与许多细胞内膜事件;然而,它们在脂滴中的确切作用在很大程度上仍未被探索。在这里,我们系统地研究了果蝇 Rab 家族蛋白在幼虫脂肪组织(脂肪体)中脂质储存中的作用。发现 Rab32 和其他几种 Rab 影响脂滴的大小和脂质水平。进一步的研究表明,Rab32 和 Rab32 GEF/Claret 可能参与自噬,从而影响脂质储存。自噬途径中的几个成分的功能丧失突变对脂质储存也有类似的影响。这些结果突出了 Rab 在调节脂质代谢中的潜在功能。