The protein YWHAE (14-3-3 epsilon) in spermatozoa is essential for male fertility.
The protein YWHAE (14-3-3 epsilon) in spermatozoa is essential for male fertility.
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DOI：
10.1111/andr.12865
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发表时间：
2021-01
期刊：
影响因子：
4.5
通讯作者：
Vijayaraghavan S
中科院分区：
文献类型：
--
作者：
Eisa A;Dey S;Ignatious A;Nofal W;Hess RA;Kurokawa M;Kline D;Vijayaraghavan S
精子发生是一个复杂的生物学过程，在精子发生过程中，蛋白质的合成和激活调节减数分裂和细胞分化。14-3-3蛋白是在真核细胞中激酶信号传导，特别是细胞周期和凋亡调控中起重要作用的衔接蛋白。14-3-3家族蛋白由7个基因（β、ε、γ、η、θ/τ、ζ和σ）编码，共有7个同工型。14-3-3异构体已被证明在包括睾丸在内的几个组织中有许多相互作用的伙伴。虽然已知14-3-3蛋白在睾丸和精子的功能中表达，但七种同工异构体中的每一种的作用尚不清楚。本研究探讨了14-3-3η和14-3-3ε同工型在精子发生中的作用。为了研究14-3-3η和14-3-3ε在精子发生中的体内功能，我们分别对14-3-3η和14-3-3ε亚型（CKO和GKO）产生了睾丸特异性和全局敲除小鼠。计算机辅助精液分析用于评估精子活力，而免疫组织化学研究用于检查精子发生。小鼠睾丸中存在14-3-3η和14-3-3ε两种异构体，但精子中只表达14-3-3ε，而不表达14-3-3η。缺失14-3-3 3η的小鼠正常且可生育，而缺失14-3-3ε CKO和GKO的雄鼠则表现为不育。14-3-3ε CKO小鼠精子数低，异常精子增多。14-3-3ε敲除精子活力低于对照组。在14-3-3ε CKO小鼠的精子中，糖原合成酶激酶3和PP1γ2的磷酸化也出现了降低，这表明14-3-3ε在精子发生、精子活力和生育能力中起着特定的作用。这是第一次证明在7个14-3-3亚型中，14-3-3ε对正常精子功能和男性生育能力至关重要。
Spermatogenesis is a complex biological process highlighted by synthesis and activation of proteins that regulate meiosis and cellular differentiation occur during spermatogenesis. 14-3-3 proteins are adaptor proteins that play critical roles in kinase signaling, especially for regulation of cell cycle and apoptosis in eukaryotic cells. There are seven isoforms of the 14-3-3 family proteins encoded by seven genes (β,ε, γ, η, θ/τ, ζ and σ). 14-3-3 isoforms have been shown to have many interacting partners in several tissues including testis. While it is known that 14-3-3 proteins are expressed in the functions of testis and spermatozoon, the role for each of the seven isoforms is not known. In this study, we investigated the roles of 14-3-3η and 14-3-3ε isoforms in spermatogenesis. To study the in vivo function of 14-3-3η and 14-3-3ε in spermatogenesis, we generated testis-specific and global knockout mice for each of 14-3-3η and 14-3-3ε isoforms (CKO and GKO, respectively). Computer-assisted semen analysis was used to assess sperm motility, while immunohistochemical studies were conducted to check spermatogenesis. Although both 14-3-3η and 14-3-3ε isoforms were present in mouse testis, only the expression of 14-3-3ε, but not 14-3-3η, was detected in spermatozoa. Mice lacking 14-3-3η were normal and fertile while 14-3-3ε CKO and GKO males showed infertility. Low sperm count with higher abnormal spermatozoa was seen in 14-3-3ε CKO mice. The motility of 14-3-3ε knockout spermatozoa was lower than that of the control. A reduction in the phosphorylation of both glycogen synthase kinase 3 and PP1γ2 was also seen in spermatozoa from 14-3-3ε CKO mice, suggesting a specific role of 14-3-3ε in spermatogenesis, sperm motility, and fertility. This is the first demonstration that of the seven 14-3-3 isoforms, 14-3-3ε is essential for normal sperm function and male fertility.
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