Meiosis I progression in spermatogenesis requires a type of testis-specific 20S core proteasome

• Published in: Nature communications 2019-07, Vol.10 (1), p.3387-11, Article 3387
• Main Authors: Zhang, Qianting, Ji, Shu-Yan, Busayavalasa, Kiran, Shao, Jingchen, Yu, Chao
• Format: Article
• Language: English
• Subjects: 13/1; 13/51; 14/19; 38/22; 45/41; 631/136/2434; 631/80/641; 64/60; activator pa28; Animals; Cell Division - genetics; chromatin; chromosome synapsis; complexes; Degradation; Developmental Biology; dmc1; failure; Female; Gametocytes; genes; Histones; Humanities and Social Sciences; Infertility; Male; Meiosis; Meiotic Prophase I - genetics; mice lacking; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; multidisciplinary; Pachytene; Pachytene Stage - genetics; Prophase; Protamine; Proteasome Endopeptidase Complex - genetics; Proteasome Endopeptidase Complex - metabolism; Proteasomes; Protein Subunits - genetics; Protein Subunits - metabolism; Proteins; repair; Science; Science & Technology - Other Topics; Science (multidisciplinary); Spermatocytes; Spermatocytes - enzymology; Spermatocytes - metabolism; Spermatogenesis; Spermatogenesis - genetics; Spermiogenesis; Testes; Testis - enzymology; Ubiquitination; Utvecklingsbiologi
• ISSN: 2041-1723; 2041-1723
• 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. Proteasomal degradation is required for the progression of spermatogenesis. Here the authors demonstrate that deletion of the testis-specific proteasome subunit PMSA8 leads to stabilization of the meiotic proteins RAD51 and RPA1 and a spermatogenic block at M-phase of meiosis I.