Cermelli Silvia, Guo Yi, Gross Steven P, Welte Michael A
Department of Developmental and Cell Biology, 2222 Natural Sciences I, University of California, Irvine, Irvine, California 92697, USA.
Curr Biol. 2006 Sep 19;16(18):1783-95. doi: 10.1016/j.cub.2006.07.062.
Lipid droplets are ubiquitous organelles that are among the basic building blocks of eukaryotic cells. Despite central roles for cholesterol homeostasis and lipid metabolism, their function and protein composition are poorly understood.
We purified lipid droplets from Drosophila embryos and analyzed the associated proteins by capillary LC-MS-MS. Important functional groups include enzymes involved in lipid metabolism, signaling molecules, and proteins related to membrane trafficking. Unexpectedly, histones H2A, H2Av, and H2B were present. Using biochemistry, genetics, real-time imaging, and cell biology, we confirm that roughly 50% of certain embryonic histones are physically attached to lipid droplets, a localization conserved in other fly species. Histone association with droplets starts during oogenesis and is prominent in early embryos, but it is undetectable in later stages or in cultured cells. Histones on droplets are not irreversibly trapped; quantitation of droplet histone levels and transplantation experiments suggest that histones are transferred from droplets to nuclei as development proceeds. When this maternal store of histones is unavailable because lipid droplets are mislocalized, zygotic histone production starts prematurely.
Because we uncover a striking proteomic similarity of Drosophila droplets to mammalian lipid droplets, Drosophila likely provides a good model for understanding droplet function in general. Our analysis also reveals a new function for these organelles; the massive nature of histone association with droplets and its developmental time-course suggest that droplets sequester maternally provided proteins until they are needed. We propose that lipid droplets can serve as transient storage depots for proteins that lack appropriate binding partners in the cell. Such sequestration may provide a general cellular strategy for handling excess proteins.
脂滴是普遍存在的细胞器，是真核细胞的基本组成部分之一。尽管胆固醇稳态和脂质代谢发挥着核心作用，但人们对其功能和蛋白质组成了解甚少。
我们从果蝇胚胎中纯化了脂滴，并通过毛细管液相色谱-串联质谱分析了相关蛋白质。重要的功能组包括参与脂质代谢的酶、信号分子以及与膜运输相关的蛋白质。出乎意料的是，组蛋白H2A、H2Av和H2B也存在。通过生物化学、遗传学、实时成像和细胞生物学方法，我们证实约50%的某些胚胎组蛋白与脂滴物理结合，这种定位在其他果蝇物种中也保守存在。组蛋白与脂滴的结合始于卵子发生过程中，并在早期胚胎中显著，但在后期阶段或培养细胞中无法检测到。脂滴上的组蛋白并非不可逆地被困住；对脂滴组蛋白水平的定量分析和移植实验表明，随着发育的进行，组蛋白从脂滴转移到细胞核。当由于脂滴定位错误而无法获得这种母源组蛋白储备时，合子组蛋白的产生会过早开始。
由于我们发现果蝇脂滴与哺乳动物脂滴在蛋白质组学上有显著相似性，果蝇可能是一个总体上理解脂滴功能的良好模型。我们的分析还揭示了这些细胞器的一项新功能；组蛋白与脂滴结合的大量性及其发育时间进程表明，脂滴隔离母源提供的蛋白质直至需要时。我们提出脂滴可以作为细胞中缺乏合适结合伴侣的蛋白质的临时储存库。这种隔离可能为处理过量蛋白质提供一种普遍的细胞策略。
