PSMA8-Containing 20S Proteasome Regulates Spermiogenesis and Male Fertility

Proteasome experiences sophisticated dynamics in types, quantities, and activities during spermiogenesis. However, the physiological importance of proteasomal degradation in mammalian spermiogenesis remains largely unknown. Here, we report that the PSMA8-containing spermato-20S proteasome (s20S) is required for spermiogenesis and male fertility in mice. In a mutant mouse model that the C-terminal 30-amino-acid (C30) of PSMA8 is substituted by PSMA7-C30, the resulting PSMA8^7C30 protein is unstable, which further disrupts the assembly of s20S and subcellular localization of 19S regulatory particle in testes. Psma8^7C30 males could produce round spermatids, but sperm formation is delayed and abnormal, exhibiting a phenotype of oligoasthenoteratozoospermia. s20S is required for the ubiquitination-dependent proteasomal degradation of a group of proteins in elongating spermatids. These s20S-mediated degradation events are essential for liquid-liquid phase separation of FXR1 and thereby translational-activation of its substrates. Taken together, these findings provide an in vivo evidence of protein homeostasis control in spermiogenesis in mammals.