O-GlcNAc transferase plays a non-catalytic role in C. elegans male fertility

Animal behavior is influenced by the competing drives to maintain energy and to reproduce. The balance between these evolutionary pressures and how nutrient signaling pathways intersect with mating remains unclear. The nutrient sensor O-GlcNAc transferase, which post-translationally modifies intracellular proteins with a single monosaccharide, is responsive to cellular nutrient status and regulates diverse biological processes. Though essential in most metazoans, O-GlcNAc transferase (ogt-1) is dispensable in Caenorhabditis elegans, allowing genetic analysis of its physiological roles. Compared to control, ogt-1 males had a four-fold reduction in mean offspring, with nearly two thirds producing zero progeny. Interestingly, we found that ogt-1 males transferred sperm less often, and virgin males had reduced sperm count. ogt-1 males were also less likely to engage in mate-searching and mate-response behaviors. Surprisingly, we found normal fertility for males with hypodermal expression of ogt-1 and for ogt-1 strains with catalytic-dead mutations. This suggests OGT-1 serves a non-catalytic function in the hypodermis impacting male fertility and mating behavior. This study builds upon research on the nutrient sensor O-GlcNAc transferase and demonstrates a role it plays in the interplay between the evolutionary drives for reproduction and survival. Author summary Animals must make decisions on whether to engage in reproduction or to conserve energy. These decisions must take into account the energy available to the animal, therefore making the nutrient sensing enzyme OGT of particular interest. In response to nutrient levels in the cell, OGT transfers the GlcNAc sugar onto proteins to regulate their function. OGT is implicated in many human diseases including diabetes, cancer, and X-linked intellectual disability. By deleting the gene encoding OGT in the nematode C. elegans, we show OGT is required for male fertility. We assessed the behavior of these mutant male worms and found they are less likely to seek mates. Surprisingly, expressing OGT specifically in the hypodermis was able to raise male fertility and restore behavior to normal levels. In addition, mutations which prevent OGT from transferring GlcNAc do not negatively impact fertility, suggesting a different function of OGT is necessary in this process. Our study demonstrates that OGT is important in critical behavioral decisions and that further investigation in C. elegans may help reveal new functions of the enzyme.