Luo Maowu, Li Dong, Wang Zhiming, Guo Wei, Kang Le, Zhou Shutang
From the State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101.
the University of Chinese Academy of Sciences, Beijing 100049, China.
J Biol Chem. 2017 May 26;292(21):8823-8834. doi: 10.1074/jbc.M117.780957. Epub 2017 Mar 29.
Juvenile hormone (JH) has a well known role in stimulating insect vitellogenesis ( yolk deposition) and oocyte maturation, but the molecular mechanisms of JH action in insect reproduction are unclear. The 78-kDa glucose-regulated protein (Grp78) is a heat shock protein 70-kDa family member and one of the most abundant chaperones in the endoplasmic reticulum (ER) where it helps fold newly synthesized peptides. Because of its prominent role in protein folding, and also ER stress, we hypothesized that might be involved in fat body cell homeostasis and vitellogenesis and a regulatory target of JH. We report here that the migratory locust possesses two genes that are differentially regulated by JH. We found that is regulated by JH through Mcm4/7-dependent DNA replication and polyploidization, whereas expression is directly activated by the JH-receptor complex comprising methoprene-tolerant and Taiman proteins. Interestingly, expression in the fat body is about 10-fold higher than that of Knockdown of either or significantly reduced levels of vitellogenin (Vg) protein, accompanied by retarded maturation of oocytes. Depletion of both and resulted in ER stress and apoptosis in the fat body and in severely defective Vg synthesis and oocyte maturation. These results indicate a crucial role of Grp78 in JH-dependent vitellogenesis and egg production. The presence and differential regulation of two genes in likely help accelerate the production of this chaperone in the fat body to facilitate folding of massively synthesized Vg and other proteins.
保幼激素(JH)在刺激昆虫卵黄生成(卵黄沉积)和卵母细胞成熟方面具有众所周知的作用,但 JH 在昆虫繁殖中的作用分子机制尚不清楚。78 kDa 的葡萄糖调节蛋白(Grp78)是热休克蛋白 70 kDa 家族成员,也是内质网(ER)中最丰富的伴侣蛋白之一,它在内质网中帮助新合成的肽折叠。由于其在蛋白质折叠以及内质网应激中发挥的重要作用,我们推测 Grp78 可能参与脂肪体细胞稳态和卵黄生成,并且是 JH 的一个调节靶点。我们在此报告,飞蝗拥有两个受 JH 差异调节的 Grp78 基因。我们发现 Grp78-1 受 JH 通过 Mcm4/7 依赖性 DNA 复制和多倍体化进行调节,而 Grp78-2 的表达由包含抗保幼激素和泰曼蛋白的 JH 受体复合物直接激活。有趣的是,脂肪体中 Grp78-2 的表达比 Grp78-1 高约 10 倍。敲低 Grp78-1 或 Grp78-2 均显著降低卵黄原蛋白(Vg)水平,同时伴随着卵母细胞成熟延迟。Grp78-1 和 Grp78-2 均缺失导致脂肪体中的内质网应激和细胞凋亡,以及严重缺陷的 Vg 合成和卵母细胞成熟。这些结果表明 Grp78 在 JH 依赖性卵黄生成和产卵中起关键作用。飞蝗中两个 Grp78 基因的存在和差异调节可能有助于加速脂肪体中这种伴侣蛋白的产生,以促进大量合成的 Vg 和其他蛋白质的折叠。