Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, SE-40530, Sweden.
Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
Nat Commun. 2019 Jul 29;10(1):3387. doi: 10.1038/s41467-019-11346-y.
Spermatogenesis is tightly regulated by ubiquitination and proteasomal degradation, especially during spermiogenesis, in which histones are replaced by protamine. However, the functions of proteasomal activity in meiosis I and II remain elusive. Here, we show that PSMA8-associated proteasomes are essential for the degradation of meiotic proteins and the progression of meiosis I during spermatogenesis. PSMA8 is expressed in spermatocytes from the pachytene stage, and assembles a type of testis-specific core proteasome. Deletion of PSMA8 decreases the abundance of proteasome in testes. Meiotic proteins that are normally degraded at late prophase I, such as RAD51 and RPA1, remain stable in PSMA8-deleted spermatocytes. Moreover, PSMA8-null spermatocytes exhibit delayed M-phase entry and are finally arrested at this stage, resulting in male infertility. However, PSMA8 is neither expressed nor required for female meiotic progression. Thus, meiosis I progression in spermatogenesis, particularly entry into and exit from M-phase, requires the proteasomal activity of PSMA8-associated proteasomes.
精子发生受到泛素化和蛋白酶体降解的严格调控，尤其是在精子发生过程中，组蛋白被鱼精蛋白取代。然而，蛋白酶体活性在减数分裂 I 和 II 中的功能仍然难以捉摸。在这里，我们表明 PSMA8 相关的蛋白酶体对于减数分裂蛋白的降解和精子发生过程中减数分裂 I 的进展是必不可少的。PSMA8 在从粗线期开始的精母细胞中表达，并组装一种睾丸特异性核心蛋白酶体。PSMA8 的缺失会降低睾丸中蛋白酶体的丰度。正常在前期 I 晚期降解的减数分裂蛋白，如 RAD51 和 RPA1，在 PSMA8 缺失的精母细胞中保持稳定。此外，PSMA8 缺失的精母细胞表现出 M 期进入延迟，最终停滞在这个阶段，导致男性不育。然而，PSMA8 在雌性减数分裂进展中既不表达也不需要。因此，精子发生中的减数分裂 I 进展，特别是进入和退出 M 期，需要 PSMA8 相关蛋白酶体的蛋白酶体活性。
