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Sequestration to lipid droplets promotes histone availability by preventing turnover of excess histones
bioRxiv - Cell Biology Pub Date : 2020-08-06 , DOI: 10.1101/2020.08.06.237164
Roxan A. Stephenson , Jonathon M. Thomalla , Lili Chen , Petra Kolkhof , Mathias Beller , Michael A. Welte

Because dearth and overabundance of histones result in cellular defects, histone synthesis and demand are typically tightly coupled. In Drosophila embryos, histones H2B/H2A/H2Av accumulate on lipid droplets (LDs), cytoplasmic fat storage organelles. Without this binding, maternally provided H2B/H2A/H2Av are absent; however, the molecular basis of how LDs ensure histone storage is unclear. Using quantitative imaging, we uncover when during oogenesis these histones accumulate, and which step of accumulation is LD-dependent. LDs originate in nurse cells and are transported to the oocyte. Although H2Av accumulates on LDs in nurse cells, the majority of the final H2Av pool is synthesized in oocytes. LDs promote intercellular transport of the histone-anchor Jabba and thus its presence in the ooplasm. Jabba prevents ooplasmic H2Av from degradation, safeguarding the H2Av stockpile. Our findings provide insight into the mechanism for establishing histone stores during Drosophila oogenesis and shed light on the function of LDs as protein-sequestration sites.

中文翻译:

隔离脂质液滴可通过防止过量组蛋白的周转来促进组蛋白的利用

由于组蛋白的缺乏和过多会导致细胞缺陷,因此组蛋白的合成和需求通常紧密结合。在果蝇胚胎中,组蛋白H2B / H2A / H2Av积累在脂滴(LDs)和细胞质脂肪储存细胞器上。如果没有这种结合,则缺乏母体提供的H2B / H2A / H2Av;然而,尚不清楚LD如何确保组蛋白存储的分子基础。使用定量成像,我们发现在卵子发生过程中这些组蛋白何时累积,以及累积的哪一步是LD依赖性的。LDs起源于护士细胞,并被转运至卵母细胞。尽管H2Av积累在护士细胞的LDs上,但大多数最终H2Av库是在卵母细胞中合成的。LDs促进组蛋白锚Jabba的细胞间运输,并因此促进其在卵质中的存在。Jabba可防止卵质H2Av降解,保护H2Av库存。我们的发现为果蝇卵子发生期间建立组蛋白存储的机制提供了见识,并阐明了LDs作为蛋白质螯合位点的功能。
更新日期:2020-08-08
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