SIGNAL TRANSDUCTIONS AT FERTILIZATION

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This ongoing project is concerned with the signalling mechanisms by which fertilization causes an egg to begin development. The project is focused on the earliest events of this process, which occur at the egg plasma membrane. These membrane events cause a rise in intracellular Ca2+, which in turn causes many subsequent developmental processes. Ca2+ release at fertilization occurs as a consequence of the action of the phospholipase C family of enzymes, which produce inositol 1,4,5- trisphosphate (IP3) from the membrane lipid phosphatidylinositol 4,5- bisphosphate (PIP2); PIP2 itself is produced by PIP kinases. Recent studies have shown that in echinoderm eggs, Ca2+ release is initiated by a signalling pathway involving the sequential activation of a Src family kinase and phospholipase C-gamma. In mammalian fertilization, the sequence of events leading to IP3 production is unknown. We propose to investigate the signalling mechanisms by which a Src family kinase is activated at fertilization of echinoderm eggs, and to investigate the possible roles of Src family kinases and PIP kinases in the signalling pathway leading to Ca2+ release at fertilization of mammalian eggs. The long term objective of these studies is to understand how the earliest events of sperm-egg interaction result in egg activation at fertilization. The significance of this work to the study of human reproduction is in providing the basic science background that underlies clinical advances.