2012年10月19日 讯 /生物谷BIOON/ --组蛋白是将DNA分子组装成染色体所需的蛋白。它们长期代表着生物学上一种经典的平衡行为：组蛋白太少会导致DNA损伤，而太多对细胞是有毒性的。
在一项新的研究中，来自美国罗切斯特大学的研究人员揭示了脂滴的一种新作用，这会让人们对组蛋白平衡概念发生根本性变化。
以前的果蝇研究表明大量的组蛋白位于脂滴---与脂肪储存相关联的结构---上。尽管先前有人猜测这些脂滴为组蛋白提供一种安全的临时性的储存场所，但是科学家们却没有明确的证据来证实这种观点，而且也没理解组蛋白如何附着到这些脂滴的表面上。
生物学副教授Michael Welte说，“研究人员发现脂滴是一种组蛋白的容纳场所，从而使得细胞在需要组蛋白的准确时间里获得它们来进行染色体组装。我们也发现当胚胎中不存在脂滴结合的组蛋白时，染色体的结构存在障碍而导致死亡。”
Welte和他的研究团队通过鉴定出被称作Jabba的蛋白而作出这些结论的，这是因为这种特异性的分子将组蛋白锚定在脂滴的表面上。相关研究结果将在下月刊登在Current Biology期刊上。
没有结合到DNA上的组蛋白长期被认为对细胞是有毒性的，这就促使它们被细胞降解掉。这项研究证实组蛋白结合到脂滴上能够保护它们，同时将它们储存起来以便用于随后的染色体组装。
鉴于有证据表明在包括人类在内的多种有机体中，组蛋白和其他蛋白与脂滴结合在一起，因此Welte相信在未来，这项研究可能具有重要的医学意义。
doi: 10.1016/j.cub.2012.09.018
PMC:
PMID:
Lipid Droplets Control the Maternal Histone Supply of Drosophila Embryos
Zhihuan Li, Katharina Thiel, Peter J. Thul, Mathias Beller, Ronald P. Kühnlein, Michael A. Welte
Background Histones are essential for chromatin packing, yet free histones not incorporated into chromatin are toxic. While in most cells multiple regulatory mechanisms prevent accumulation of excess histones, early Drosophila embryos contain massive extranuclear histone stores, thought to be essential for development. Excess histones H2A, H2B, and H2Av are bound to lipid droplets, ubiquitous fat storage organelles especially abundant in embryos. It has been proposed that sequestration on lipid droplets allows safe transient storage of supernumerary histones. Results Here, we critically test this sequestration hypothesis. We find that histones are anchored to lipid droplets via the previously uncharacterized protein Jabba: Jabba localizes to droplets, coimmunoprecipitates with histones, and is necessary to recruit histones to droplets. Jabba mutants lack the maternal H2A, H2B, and H2Av deposits altogether; presumably, these deposits are eliminated unless sequestered on droplets. Jabba mutant embryos compensate for this histone deficit by translating maternal histone mRNAs. However, when histone expression is mildly compromised, the maternal histone protein deposits are essential for proper early mitoses and for viability. Conclusions A growing number of proteins from other cellular compartments have been found to transiently associate with lipid droplets. Our studies provide the first insight into mechanism and functional relevance of this sequestration. We conclude that sequestration on lipid droplets allows embryos to build up extranuclear histone stores and provides histones for chromatin assembly during times of high demand. This work reveals a novel aspect of histone metabolism and establishes lipid droplets as functional storage sites for unstable or detrimental proteins.
