Interactions between the WEE-1.3 kinase and the PAM-1 aminopeptidase in oocyte maturation and the early C. elegans embryo.

Dorothy Benton, Eva C Jaeger, Arielle Kilner, Ashley Kimble, Josh Lowry, Emily M Schleicher, Kaiden M Power, Danielle Uibel, Caprice Eisele, Bruce Bowerman, Rebecca Lyczak

G3 (Bethesda, Md.) 2021 Apr 15

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Puromycin-sensitive aminopeptidases are found across phyla and are known to regulate the cell-cycle and play a protective role in neurodegenerative disease. PAM-1 is a puromycin-sensitive aminopeptidase important for meiotic exit and polarity establishment in the one-cell Caenorhabditis elegans embryo. Despite conservation of this aminopeptidase, little is known about its targets during development. In order to identify novel interactors, we conducted a suppressor screen and isolated four suppressing mutations in three genes that partially rescued the maternal-effect lethality of pam-1 mutants. Suppressed strains show improved embryonic viability and polarization of the anterior-posterior axis. We identified a missense mutation in wee-1.3 in one of these suppressed strains. WEE-1.3 is an inhibitory kinase that regulates maturation promoting factor. Although the missense mutation suppressed polarity phenotypes in pam-1, it does so without restoring centrosome-cortical contact or altering the cortical actomyosin cytoskeleton. To see if PAM-1 and WEE-1.3 interact in other processes, we examined oocyte maturation. Although depletion of wee-1.3 causes sterility due to precocious oocyte maturation, this effect was lessened in pam-1 worms, suggesting that PAM-1 and WEE-1.3 interact in this process. Levels of WEE-1.3 were comparable between wild-type and pam-1 strains, suggesting that WEE-1.3 is not a direct target of the aminopeptidase. Thus, we have established an interaction between PAM-1 and WEE-1.3 in multiple developmental processes and have identified suppressors that are likely to further our understanding of the role of puromycin-sensitive aminopeptidases during development. © The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.

Citation

Dorothy Benton, Eva C Jaeger, Arielle Kilner, Ashley Kimble, Josh Lowry, Emily M Schleicher, Kaiden M Power, Danielle Uibel, Caprice Eisele, Bruce Bowerman, Rebecca Lyczak. Interactions between the WEE-1.3 kinase and the PAM-1 aminopeptidase in oocyte maturation and the early C. elegans embryo. G3 (Bethesda, Md.). 2021 Apr 15;11(4)