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。该项目的重点是这一过程的最早期事件，发生在卵质膜上。这些膜事件引起细胞内Ca 2+的升高，这反过来又引起许多随后的发育过程。受精时的Ca 2+释放是磷脂酶C家族酶作用的结果，磷脂酶C家族酶从膜脂磷脂酰肌醇4，5-二磷酸（PIP 2）产生肌醇1，4，5-三磷酸（IP 3）; PIP 2本身由PIP激酶产生。最近的研究表明，在棘皮动物卵中，Ca 2+的释放是由一个信号通路启动的，该通路涉及Src家族激酶和磷脂酶C-γ的顺序激活。在哺乳动物受精中，导致IP 3产生的事件顺序是未知的。我们建议调查Src家族激酶激活棘皮动物卵受精的信号传导机制，并调查Src家族激酶和PIP激酶在哺乳动物卵受精时导致Ca 2+释放的信号传导途径中的可能作用。这些研究的长期目标是了解精子-卵子相互作用的最早期事件如何导致受精时的卵子激活。这项工作对人类生殖研究的重要性在于提供了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.