Collaboration within the M1 aminopeptidase family promotes reproductive success in Caenorhabditis elegans

Mutations of the puromycin-sensitive aminopeptidase (Psa) orthologs of flies, mice, and plants result in meiotic errors and reduced embryonic viability. Genetic lesions of the Caenorhabditis elegans ortholog of Psa, pam-1, similarly result in dramatic reductions of worm fecundity. The gonads of animals harboring mutant pam-1 alleles display expanded populations of pachytene germinal nuclei and delayed nucleolar disassembly in the developing oocytes, phenotypes that ultimately hinder embryonic viability and overall brood sizes. PAM-1 is a member of the M1 aminopeptidase family and shares a high amount of homology with its M1 paralogs. Comparative analysis of the M1 aminopeptidase family reveals that only nine (including PAM-1) of the 17 annotated M1 aminopeptidases are predicted to be catalytically active. Interestingly, we demonstrate that three of these active M1 paralogs have roles independent of PAM-1 in promoting gametogenesis and fecundity. Simultaneous inhibition of pam-1 and M1 paralogs produces synergistic decreases in overall brood sizes and embryonic viability, exacerbates the germinal phenotypes of pachytene extension and delayed nucleolar disassembly, and unmasks previously hidden phenotypes. Our data suggests that the interdependent functions of multiple M1 aminopeptidases are necessary for reproductive success in C. elegans and lend further credence to the redundant composition of an evolutionarily conserved enzyme family.