Dependence of sperm structural and functional integrity on testicular calcineurin isoform PPP3R2 expression
Dependence of sperm structural and functional integrity on testicular calcineurin isoform PPP3R2 expression
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精子结构和功能完整性对睾丸钙调神经磷酸酶亚型 PPP3R2 表达的依赖性
DOI：
10.1093/jmcb/mjz115
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发表时间：
2020-07-01
影响因子：
5.5
通讯作者：
Ding, Zhide
中科院分区：
文献类型：
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作者：
Liu, Yue;Zhang, Chujun;Ding, Zhide
离开睾丸后，哺乳动物的精子在附睾中经历了顺序成熟过程，然后在通过女性生殖道运动过程中进行了电容。这些表型变化与蛋白质磷酸化和膜重塑的修饰有关，这对于精子获得前向运动并诱导施肥是必需的。但是，精子成熟和电容的基础机制仍未完全了解。在此，我们表明PPP3R2是蛋白质磷酸酶3的睾丸特异性调节亚基（睾丸中钙调蛋白的同工型），对于精子成熟和电容至关重要。小鼠中PPP3R2的敲除，由于精子运动障碍和形态缺陷而导致男性不育。一个非常值得注意的变化包括精子膜刚度的增加。此外，PPP3R2通过（i）通过（i）环形的膜扩散屏障功能调节精子成熟和电容，（ii）在精子电容期间促进胆固醇外排。综上所述，PPP3R2在调节胆固醇外排和介导精子成熟和电容过程中膜重塑的动态控制方面起着至关重要的作用。
Abstract After leaving the testis, mammalian sperm undergo a sequential maturation process in the epididymis followed by capacitation during their movement through the female reproductive tract. These phenotypic changes are associated with modification of protein phosphorylation and membrane remodeling, which is requisite for sperm to acquire forward motility and induce fertilization. However, the molecular mechanisms underlying sperm maturation and capacitation are still not fully understood. Herein, we show that PPP3R2, a testis-specific regulatory subunit of protein phosphatase 3 (an isoform of calcineurin in the testis), is essential for sperm maturation and capacitation. Knockout of Ppp3r2 in mice leads to male sterility due to sperm motility impairment and morphological defects. One very noteworthy change includes increases in sperm membrane stiffness. Moreover, PPP3R2 regulates sperm maturation and capacitation via (i) modulation of membrane diffusion barrier function at the annulus and (ii) facilitation of cholesterol efflux during sperm capacitation. Taken together, PPP3R2 plays a critical role in modulating cholesterol efflux and mediating the dynamic control of membrane remodeling during sperm maturation and capacitation.