Non-Redundant Essential Roles of Proteasomal Ubiquitin Receptors Rpn10 and Rpn13 in Germ Cell Formation and Fertility.

Abstract

Primordial germ cells (PGCs) undergo proliferation, migration, and sexual differentiation to produce gonocytes, which eventually generate germ cells. The proteasome, which degrades most cellular proteins, is a protein complex with dozens of subunits. The proteasomal ubiquitin receptors Rpn10 and Rpn13 have been shown to play partially overlapping roles in binding ubiquitin chains in vitro and in liver function in vivo. However, the specific role of Rpn10 and Rpn13 in germ cell production remains unclear. We show here that Rpn10 and Rpn13 are each essential for germ cell production and fertility. The conditional deletion of either Rpn10 or Rpn13 in PGCs results in infertility in both male and female mice. Germ cells in testes and ovaries all decreased dramatically in the Rpn13 conditional knockout (cKO) mice. Specifically, the deletion of Rpn13 in PGCs disrupts the assembly of the 26S proteasome, reduces the number of PGCs, and blocks the meiosis of spermatocytes at the zygotene stage during prophase I; on the other hand, the deletion of Rpn10 in PGCs sharply reduces PGC migration. These results are important for understanding the roles of Rpn10 and Rpn13 in germ cell development and related reproductive diseases.