BioProject

The molecular mechanisms that govern the metabolic commitment to reproduction, which often occurs at the expense of the soma, remain poorly understood. More...

The molecular mechanisms that govern the metabolic commitment to reproduction, which often occurs at the expense of the soma, remain poorly understood. We identified the C. elegans F-box protein FBXL-5 as a negative regulator of maternal provisioning of vitellogenin lipoproteins, which mediate the transfer of intestinal lipids to the germline. Mutations in fbxl-5 partially suppress the vitellogenesis defects observed in the heterochronic mutants lin-4 and lin-29, both of which ectopically express fbxl-5 at the adult developmental stage. FBXL-5 functions cell-autonomously to negatively regulate expression of the vitellogenin genes; and consistently, intestinal over-expression of FBXL-5 is sufficient to inhibit vitellogenesis, impair overall lipid homeostasis, and reduce lifespan. Our epistasis analyses suggest that fbxl-5 functions in concert with cul-6, a cullin gene, and the Skp1-related genes skr-3 and skr-5 to regulate vitellogenesis. Additionally, fbxl-5 acts genetically upstream of rict-1, which encodes the core mTORC2 protein Rictor, to govern vitellogenesis. Together, our results reveal an unexpected role for a SCF ubiquitin-ligase complex in controlling intestinal lipid homeostasis by tuning mTORC2 activity. Overall design: The mRNAs of wild-type, lin-29(n333), fbxl-5(rhd43), and rict-1(mg360) day 1 adult animals were profiled by high-throughput sequencing, in triplicate. Less...