Lipid droplets control the maternal histone supply of Drosophila embryos.
Lipid droplets control the maternal histone supply of Drosophila embryos.
复制标题
DOI：
10.1016/j.cub.2012.09.018
复制
发表时间：
2012-11-20
期刊：
影响因子：
9.2
通讯作者：
Welte, Michael A.
中科院分区：
文献类型：
--
作者：
Li, Zhihuan;Thiel, Katharina;Thul, Peter J.;Beller, Mathias;Kuehnlein, Ronald P.;Welte, Michael A.
组蛋白对于染色质的包装是必不可少的，但没有结合到染色质中的游离组蛋白是有毒的。虽然在大多数细胞中，多种调节机制可以防止过量的组蛋白积累，但早期果蝇胚胎包含大量的核外组蛋白存储，被认为是发育所必需的。过量的组蛋白H_2A、H_2B和H_2Av与脂滴结合，脂滴是普遍存在的脂肪储存细胞器，在胚胎中尤其丰富。有人提出，脂滴上的隔离可以安全地瞬时储存多余的组蛋白。在这里，我们批判性地检验这一自动减支假说。我们发现，组蛋白通过以前未鉴定的蛋白Jabba固定在脂滴上：Jabba定位于液滴，与组蛋白共免疫沉淀，是向液滴募集组蛋白所必需的。Jabba突变体完全缺乏母体的H_2A、H_2B和H_2Av沉淀物；据推测，这些沉淀物除非被隔离在液滴上，否则会被消除。Jabba突变胚胎通过翻译母体组蛋白mRNAs来弥补这种组蛋白缺陷。然而，当组蛋白表达受到轻微影响时，母体的组蛋白沉积对于正常的早期有丝分裂和生存是必不可少的。越来越多的来自其他细胞隔间的蛋白质被发现与脂滴瞬时相关。我们的研究为这种隔离的机制和功能相关性提供了第一个洞察。我们的结论是，脂滴上的隔离使胚胎能够建立核外的组蛋白存储，并在高需求时期为染色质组装提供组蛋白。这项工作揭示了组蛋白代谢的一个新方面，并建立了脂滴作为不稳定或有害蛋白质的功能存储位置。
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 extra-nuclear 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. 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, co-immunoprecipitates 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. 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 extra-nuclear histones 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.
登录
查看更多内容
影响因子：
2.3
作者：
Fujimoto, Toyoshi;Ohsaki, Yuki;Cheng, Jinglei;Suzuki, Michitaka;Shinohara, Yuki
通讯作者：
Shinohara, Yuki
DOI：
10.1073/pnas.95.7.3396
发表时间：
1998-03-31
影响因子：
11.1
作者：
An, WJ;Leuba, SH;Zlatanova, J
通讯作者：
Zlatanova, J
影响因子：
64.5
作者：
EDGAR, BA;SCHUBIGER, G
通讯作者：
SCHUBIGER, G
影响因子：
4.8
作者：
Nagai, A;Sato, T;Sumida, M
通讯作者：
Sumida, M
影响因子：
9.2
作者：
Gross, SP;Guo, Y;Welte, MA
通讯作者：
Welte, MA