SIGNAL TRANSDUCTIONS AT FERTILIZATION

这个正在进行的项目涉及受精导致卵子开始发育的信号机制。该项目的重点是发生在卵子质膜上的这一过程的最早事件。这些膜事件导致细胞内钙离子升高，进而导致许多后续的发育过程。受精时钙的释放是磷脂酶C家族作用的结果，磷脂酶C家族从膜脂磷脂酰肌醇4，5-二磷酸(PIP2)中产生肌醇1，4，5-三磷酸(IP3)；PIP2本身是由PIP激酶产生的。最近的研究表明，棘皮动物卵中，钙离子的释放是由一条信号通路启动的，该通路包括一个Src家族的激酶和磷脂酶C-γ的顺序激活。在哺乳动物受精中，导致IP3产生的事件序列尚不清楚。我们建议研究棘皮动物卵子受精时，Src家族的蛋白激酶激活的信号机制，以及在哺乳动物卵子受精时导致钙释放的信号通路中，Src家族蛋白和PIP蛋白的可能作用。这些研究的长期目标是了解精子-卵子相互作用的最早事件如何导致受精时卵子激活。这项工作对人类生殖研究的意义在于提供了支撑临床进展的基础科学背景。

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.