Lipid Signaling During Fertilization

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0110609StithAlthough the major event of fertilization is known to be the release of intracellular calcium, the exact cause of this calcium release is unknown. Activation of phospholipase C appears to be required for the release of calcium at fertilization; however, it is not known how this enzyme is activated. One possible path to activation of phospholipase C may be through another lipid signaling path. In an effort to quantify various lipid signaling paths, it has been noted that the mass of sphingomyelin, phosphatidylcholine and phosphatidylinositol decrease whereas choline, IP3, DAG and phosphatidic acid increase (phosphatidylethanolamine and phosphatidylserine do not change) during Xenopus fertilization. From these data and others, it is suggested that phospholipase D plays an important role in fertilization. Phosphatidic acid is a product of the reaction catalyzed by phospholipase D. Phosphatidic acid may be required for membrane fusion events (e.g.: sperm-egg merger, cortical granule-plasma membrane merger) and the DAG increase (since phosphatidic acid can be dephosphorylated to DAG) at fertilization. Most importantly, phosphatidic acid binds to and activates phospholipase C; thus, phosphatidic acid from sperm or that produced in the newly formed zygote may induce the central event of fertilization: the increase in intracellular calcium. Through the use of exogenous phosphatidic acid, or inhibition of phospholipase D, the role of this enzyme and the product phosphatidic acid in fertilization will be examined.