Critical roles for lipid synthesis in Caenorhabditis elegans
Watts, Jason Scott
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Multicellular organisms depend on lipids for compartmentalization of cells and organelles. Additionally, lipids are critical for energy storage, and some lipids act as potent signaling molecules. To meet these diverse needs, organisms constantly synthesize and recycle a vast array of structurally diverse lipids. We sought to discover novel roles for lipid synthesis genes and specific lipid products in multicellular organisms utilizing Caenorhabditis elegans. Using genetic knockouts and knockdowns of lipid synthesis genes, we sought to elucidate roles of specific lipids and lipid synthesis in specific tissues and stages of development. To meet these divergent needs, organisms synthesize an array of structurally variant lipids. We determined that the C. elegans holocarboxyase synthetase homolog, BPL-1 is required for polarization of the embryo and integrity of the eggshell permeability barrier. Using biotin protein blots, we found that BPL-1 biotinylates the C. elegans carboxylases POD-2, PYC-1, MCCC-1, and PCCA-1, and we demonstrated that BPL-1 was necessary for efficient fatty acid biosynthesis during normal growth. We found that functioning lipid biosynthesis machinery is required for maintaining embryo polyunsaturated fatty acid composition, and that polyunsaturated fatty acids are required for the eggshell permeability barrier. Using biotin protein blots, we found that BPL-1 biotinylates the C. elegans carboxylases POD-2, PYC-1, MCCC-1, and PCCA-1. We utilized polyunsaturated fatty acid synthesis to help develop better tissue-specific gene knockdown tools for C. elegans. And finally, we characterized a previously unknown dihydroceramide desaturase and demonstrated that buildup of dihydrosphingomyelins shortens lifespan and increases pathogen resistance. Together, these findings indicate that maintenance of lipid composition by endogenous lipid synthesis is vital for multiple aspects of biological function in multicellular organisms.