Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102.
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102.
J Biol Chem. 2018 Feb 23;293(8):2990-3002. doi: 10.1074/jbc.M117.814657. Epub 2018 Jan 11.
Lipid metabolism plays a critical role in female reproduction. During oogenesis, maturing oocytes accumulate high levels of neutral lipids that are essential for both energy production and the synthesis of other lipid molecules. Metabolic pathways within the ovary are partially regulated by protein kinases that link metabolic status to oocyte development. Although the functions of several kinases in this process are well established, the roles that many other kinases play in coordinating metabolic state with female germ cell development are unknown. Here, we demonstrate that the catalytic activity of casein kinase 2 (CK2) is essential for oogenesis. Using an unbiased biochemical screen that leveraged an unusual catalytic property of the kinase, we identified a novel CK2 substrate in the ovary, the lipid droplet-associated protein Jabba. We show that Jabba is essential for modulating ovarian lipid metabolism and for regulating female fertility in the fly. Our findings shed light on a CK2-dependent signaling pathway governing lipid metabolism in the ovary and provide insight into the long-recognized but poorly understood association between energy metabolism and female reproduction.
脂质代谢在女性生殖中起着至关重要的作用。在卵子发生过程中,成熟的卵母细胞积累高水平的中性脂质,这对于能量产生和其他脂质分子的合成都是必不可少的。卵巢内的代谢途径部分受蛋白激酶调控,这些激酶将代谢状态与卵母细胞发育联系起来。尽管该过程中几种激酶的功能已经得到很好的确立,但许多其他激酶在协调代谢状态与雌性生殖细胞发育方面的作用仍不清楚。在这里,我们证明了酪蛋白激酶 2(CK2)的催化活性对于卵子发生是必需的。我们利用激酶的一个不寻常的催化特性进行了一项无偏的生化筛选,在卵巢中鉴定到了一个新的 CK2 底物,即脂滴相关蛋白 Jabba。我们表明 Jabba 对于调节卵巢脂质代谢和调节果蝇的雌性生育能力是必需的。我们的研究结果揭示了一个 CK2 依赖性信号通路,该通路调控卵巢中的脂质代谢,并为长期以来被认识但理解不足的能量代谢与雌性生殖之间的联系提供了新的认识。