2012年10月19日 訊 /生物谷BIOON/ --組蛋白是將DNA分子組裝成染色體所需的蛋白,。它們長期代表著生物學上一種經(jīng)典的平衡行為：組蛋白太少會導致DNA損傷，而太多對細胞是有毒性的。
在一項新的研究中,，來自美國羅切斯特大學的研究人員揭示了脂滴的一種新作用,，這會讓人們對組蛋白平衡概念發(fā)生根本性變化,。
以前的果蠅研究表明大量的組蛋白位于脂滴---與脂肪儲存相關(guān)聯(lián)的結(jié)構(gòu)---上,。盡管先前有人猜測這些脂滴為組蛋白提供一種安全的臨時性的儲存場所,，但是科學家們卻沒有明確的證據(jù)來證實這種觀點，而且也沒理解組蛋白如何附著到這些脂滴的表面上,。
生物學副教授Michael Welte說,，“研究人員發(fā)現(xiàn)脂滴是一種組蛋白的容納場所，從而使得細胞在需要組蛋白的準確時間里獲得它們來進行染色體組裝,。我們也發(fā)現(xiàn)當胚胎中不存在脂滴結(jié)合的組蛋白時,，染色體的結(jié)構(gòu)存在障礙而導致死亡。”
Welte和他的研究團隊通過鑒定出被稱作Jabba的蛋白而作出這些結(jié)論的,，這是因為這種特異性的分子將組蛋白錨定在脂滴的表面上,。相關(guān)研究結(jié)果將在下月刊登在Current Biology期刊上。
沒有結(jié)合到DNA上的組蛋白長期被認為對細胞是有毒性的,，這就促使它們被細胞降解掉,。這項研究證實組蛋白結(jié)合到脂滴上能夠保護它們，同時將它們儲存起來以便用于隨后的染色體組裝,。
鑒于有證據(jù)表明在包括人類在內(nèi)的多種有機體中,，組蛋白和其他蛋白與脂滴結(jié)合在一起，因此Welte相信在未來,，這項研究可能具有重要的醫(yī)學意義,。
doi: 10.1016/j.cub.2012.09.018
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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.
