SIGNAL TRANSDUCTION MECHANISMS IN MOUSE EGG ACTIVATION

小鼠卵子受精会引发一种称为“卵子激活”的现象。 EGG的激活导致(1)皮质颗粒(CG)的刺激 胞吐作用导致透明带(ZP)的修饰 构成多精受精的块，以及(2)减数分裂的转化 细胞周期进入有丝分裂周期(有丝分裂激活)。以…为类比 分化的体细胞，精子可能通过G 蛋白介导的信号转导途径导致了 特定的第二信使/离子变化。体细胞的反应 与细胞表面受体结合的细胞到体液配体通常是 仅限于胞吐或有丝分裂反应。它的独特之处在于 卵子激活是指精子，类似于配体，诱导 在同一靶细胞中的胞吐和有丝分裂反应，即， 鸡蛋。已经证明，特定的第二信使 (1，4，5-三磷酸肌醇)或蛋白激酶C激活剂诱导 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，尽管两个CG 胞吐作用和有丝分裂激活是由受精的精子启动的， 不同的第二信使系统可以不同地被激活 调节这两种反应。尽管G蛋白介导胞吐作用和 在体细胞中的有丝分裂激活，事实上，没有定论 哺乳动物卵子激活是由G蛋白偶联介导的数据 信号转导级联。这项提案中概述的实验包括 旨在检验G蛋白与精子有关的假设-- 诱导哺乳动物卵子激活。

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.