DPAGT1-Mediated Protein N-Glycosylation Is Indispensable for Oocyte and Follicle Development in Mice
DPAGT1-Mediated Protein N-Glycosylation Is Indispensable for Oocyte and Follicle Development in Mice
复制标题
DPAGT1 介导的蛋白质 N-糖基化对于小鼠卵母细胞和卵泡发育是不可或缺的。
DOI：
10.1002/advs.202000531
复制
发表时间：
2020-06-03
期刊：
影响因子：
15.1
通讯作者：
Su, You-Qiang
中科院分区：
文献类型：
--
作者：
Li, Hui;You, Liji;Su, You-Qiang
通过N-连接糖基化对蛋白质的翻译后修饰对于许多生命过程至关重要。但是，N-糖基化对哺乳动物女性繁殖的确切贡献在很大程度上仍然不确定。在这里，DPAGT1是催化蛋白质N-糖基化的第一步的酶，被认为是小鼠卵母细胞发育必不可少的。 DPAGT1错义突变（c。497a> g;p。Asp166gly）会导致女性的不良性，而不会严重影响其他功能。由于生长卵泡的发育不良，突变女性排卵较少。由于ZP蛋白质的糖基化降低，突变卵母细胞具有薄而脆弱的Zona pellucida（ZP），并且在体外受精后表现出较差的发育能力。此外，在突变卵母细胞中加速了第一个减数分裂，这与非整倍性的升高相吻合。从机械上讲，转录组分析揭示了突变卵母细胞中卵母细胞减数分裂进展和植入前发展（例如PTTGT1，ESCO2，ORC6和NPM2）所必需的许多转录本的下调，这可能会观察到缺陷。此外，卵母细胞中DPAGT1的条件敲除概括了在DPAGT1突变女性中观察到的表型，并导致完全不孕。综上所述，这些数据表明，卵母细胞中蛋白质N-糖基化是通过对卵母细胞发育的特定控制对哺乳动物的女性生育至关重要的。
Post-translational modification of proteins by N-linked glycosylation is crucial for many life processes. However, the exact contribution of N-glycosylation to mammalian female reproduction remains largely undefined. Here, DPAGT1, the enzyme that catalyzes the first step of protein N-glycosylation, is identified to be indispensable for oocyte development in mice. Dpagt1 missense mutation (c. 497A>G; p. Asp166Gly) causes female subfertility without grossly affecting other functions. Mutant females ovulate fewer eggs owing to defective development of growing follicles. Mutant oocytes have a thin and fragile zona pellucida (ZP) due to the reduction in glycosylation of ZP proteins, and display poor developmental competence after fertilization in vitro. Moreover, completion of the first meiosis is accelerated in mutant oocytes, which is coincident with the elevation of aneuploidy. Mechanistically, transcriptomic analysis reveals the downregulation of a number of transcripts essential for oocyte meiotic progression and preimplantation development (e.g., Pttgt1, Esco2, Orc6, and Npm2) in mutant oocytes, which could account for the defects observed. Furthermore, conditional knockout of Dpagt1 in oocytes recapitulates the phenotypes observed in Dpagt1 mutant females, and causes complete infertility. Taken together, these data indicate that protein N-glycosylation in oocytes is essential for female fertility in mammals by specific control of oocyte development.