SIGNAL TRANSDUCTION MECHANISMS IN MOUSE EGG ACTIVATION

小鼠卵子的受精引发了一种称为“卵子激活”的现象。 卵激活导致（1）皮层颗粒（CG）的刺激 胞吐作用，导致透明质酸（ZP）的修饰， 构成多精受精的障碍，以及（2）减数分裂的转化 有丝分裂（mitotic activation）。 通过类似于 在体细胞分化过程中，精子可能通过G 蛋白质介导的信号转导途径，导致产生 特定的第二信使/离子变化。 躯体反应 细胞与结合细胞表面受体的体液配体的结合通常 局限于胞吐或促有丝分裂反应。 的独特之处 卵子激活是精子，它类似于配体， 在同一靶细胞中的胞吐和促有丝分裂反应，即， 鸡蛋 已经证明，特定的第二信使 （肌醇1，4，5-三磷酸）或蛋白激酶C的激活剂引起 ZP修饰与卵子激活相关，但不会导致 有丝分裂激活 这些观察表明，尽管CG 胞吐作用和有丝分裂激活由精子启动， 不同的第二信使系统可以被激活， 规范这两种反应。 虽然G蛋白介导胞吐作用， 有丝分裂激活的体细胞，有，事实上，没有定论 数据表明，哺乳动物卵子激活是由G蛋白偶联的 信号转导级联 该提案中概述的实验是 旨在验证G蛋白与精子有关的假设 诱导哺乳动物卵子活化。

Fertilization of mouse eggs initiates a phenomenon termed "egg activation". Egg activation results in (1) the stimulation of cortical granule (CG) exocytosis that results in modifications of the zona pellucida (ZP) that constitute the block to polyspermy, and (2) the conversion of a meiotic cell cycle to a mitotic one (mitotic activation). By analogy to differentiated somatic cells, the sperm may initiate these events by a G protein-mediated signal transduction pathway that results in the generation of specific second messengers/ionic changes. The responses of somatic cells to humoral ligands that bind to cell surface receptors are generally confined to either exocytotic or mitogenic responses. What is unique about egg activation is that the sperm, which is analogous to a ligand, induces both an exocytotic and mitogenic response in the same target cell, i.e., the egg. It has been demonstrated that specific second messengers (inositol 1,4,5-trisphosphate) or activators of protein kinase C elicit the ZP modifications associated with egg activation, but do not result in mitotic activation. These observations suggest that although both CG exocytosis and mitotic activation are initiated by the fertilizing sperm, different second messenger systems may be activated that differentially regulate these two responses. Although G proteins mediate exocytosis and mitogenic activation in somatic cells, there are, in fact, no conclusive data that mammalian egg activation is mediated by a G protein-coupled signal transduction cascade. The experiments outlined in this proposal are designed to test the hypothesis that G proteins are involved in sperm- induced mammalian egg activation.