emb-20 encodes a farnesyl diphosphate synthase in Caenorhabditis elegans

Oocytes grow through biosynthesis of cellular components as well as endocytosis to take up nutrients from the extracellular space. They also develop cortical granules that are exocytosed after fertilization to alter the extracellular environment. We have previously shown that defects in cortical granule formation and exocytosis cause an osmotically sensitive embryo phenotype and embryonic lethality. To identify regulators of cortical granule formation and exocytosis, we characterized a Caenorhabditis elegans emb-20(g27) mutant displaying similar phenotypes at a restrictive temperature (25 °C). The fluorescently labeled cortical granule marker, GFP::CAV-1, mainly localized to cortical granules and the plasma membrane in control oocytes at 15 °C and 25 °C and in emb-20(g27) oocytes at 15 °C. In contrast, GFP::CAV-1 largely accumulated in fine punctate structures in emb-20(g27) mutant oocytes at 25 °C. The emb-20(g27) mutants also exhibited impaired endocytic yolk uptake by oocytes. We revealed that the emb-20(g27) mutant harbors a missense mutation in the fdps-1 gene, which encodes a farnesyl diphosphate synthase in the mevalonate pathway, causing a Glu282-to-Lys substitution. Farnesyl diphosphate is an essential precursor for generating geranylgeranyl groups for the prenylation of RAB small GTPases. We found that the endoplasmic reticulum-to-Golgi transport regulator, RAB-1, and endocytic regulators, such as RAB-5, RAB-7, and RAB-11, lost their organelle localization and became diffusely distributed throughout the cytoplasm and nucleus in emb-20(g27) mutant oocytes at 25 °C, and their prenylation states were drastically affected. These results suggest that EMB-20/FDPS-1 is essential for maintaining appropriate RAB GTPase function to preserve active membrane trafficking in developing oocytes.