The F-box protein FBXL-5 governs vitellogenesis and lipid homeostasis inC. elegans

Abstract

ABSTRACTThe molecular mechanisms that govern the metabolic commitment to reproduction, which often occurs at the expense of somatic reserves, remain poorly understood. We identified theC. elegansF-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 infbxl-5partially suppress the vitellogenesis defects observed in the heterochronic mutantslin-4andlin-29,both of which ectopically expressfbxl-5at the adult developmental stage. FBXL-5 functions in the intestine to negatively regulate expression of the vitellogenin genes; and consistently, intestine-specific over-expression of FBXL-5 is sufficient to inhibit vitellogenesis, restrict lipid accumulation, and shorten lifespan. Our epistasis analyses suggest thatfbxl-5functions in concert withcul-6, a cullin gene, and the Skp1-related geneskr-3to regulate vitellogenesis. Additionally,fbxl-5acts genetically upstream ofrict-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 engaging mTORC2 signaling.