After leaving the testis, mammalian sperm undergoes a sequential maturation process in the epididymis followed by capacitation during its 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 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: (1) modulation of membrane diffusion barrier function at the annulus; (2) facilitation of cholesterol efflux during sperm capacitation. Taken together, PPP3R2 plays a critical role in modulating cholesterol efflux and mediating dynamic control of membrane remodeling during sperm maturation and capacitation.

中文翻译：

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精子结构和功能完整性对睾丸钙调神经磷酸酶同种型 PPP3R2 表达的依赖性。

离开睾丸后，哺乳动物精子在附睾中经历一个连续的成熟过程，然后在其通过女性生殖道的过程中获能。这些表型变化与蛋白质磷酸化的修饰和膜重塑有关，这是精子获得向前运动和诱导受精所必需的。然而，精子成熟和获能的分子机制仍未完全了解。在此，我们展示了 PPP3R2，蛋白质磷酸酶 3（睾丸中钙调磷酸酶的同种型）的睾丸特异性调节亚基，对于精子成熟和获能至关重要。由于精子活力障碍和形态缺陷，小鼠中 Ppp3r2 的敲除会导致雄性不育。一个非常值得注意的变化包括精子膜刚度的增加。此外，PPP3R2 通过以下方式调节精子成熟和获能：(1) 调节环处的膜扩散屏障功能；(2)促进精子获能期间胆固醇外流。总之，PPP3R2 在调节胆固醇流出和介导精子成熟和获能过程中膜重塑的动态控制方面起着关键作用。