ROLE OF ACTIN CYTOSKELETON DURING MOUSE SPERM ACROSOMAL EXOCYTOSIS

摘要 哺乳动物的精子必须经历一个称为获能的过程，才能使卵子受精。 获能使精子有能力通过启动细胞来经历快速的胞吐事件 被称为顶体胞吐，是由卵子或黄体酮的卵泡带(ZP)刺激的。 多年来，已经有几个生化事件与获能过程有关； 然而，在对获能能力的研究中仍然没有回答的问题是：什么是 使精子细胞从对ZP或ZP无反应状态转变的潜在反应或一系列反应 黄体酮刺激的顶体胞吐到准备对这些刺激做出反应的状态？我们的 初步结果表明，肌动蛋白细胞骨架在这一过程中发挥了作用。我们的长期合作 本研究的目的：阐明肌动蛋白细胞骨架调控的分子机制。 哺乳动物精子的顶体胞吐作用。在这份提案中，我们评估了建立和 精子发育过程中顶体胞吐启动状态的稳定 获能。此外，我们还将研究细胞内钙和肌动蛋白在 顶体胞吐的启动状态不稳定，导致融合的传播 顶体外膜和质膜。有几个与人类健康有关的原因 研究意义重大。例如，了解这一过程可能会导致更好的理解 对某些男性不育病例的研究和药物干预方法的发展 随着这一过程，导致了新的避孕药的出现。最重要的是，因为肌动蛋白牵涉其中 在许多类型的体细胞中发生胞吐作用时，从研究中收集的信息较少 复杂的精子系统可能会影响我们对其他器官系统分泌的理解，如 作为内分泌或消化组织。

Summary Mammalian sperm must undergo a process termed capacitation to become competent to fertilize an egg. Capacitation renders the sperm competent by priming the cells to undergo a rapid exocytotic event called acrosomal exocytosis that is stimulated by the zona pelucida (ZP) of the egg or progesterone. Over the years, several biochemical events have been associated with the capacitation process; however, the question that has remained unanswered in investigations of capacitation is: What is the underlying reaction or set of reactions that transform the sperm cell from a state unresponsive to ZP or progesterone-stimulated acrosomal exocytosis to the state primed to respond to these stimuli? Our preliminary results demonstrate that the actin cytoskeleton plays a role in this process. Our long-term goal of this research: to elucidate the molecular mechanism whereby the actin cytoskeleton controls acrosomal exocytosis in mammalian sperm. In this proposal, we evaluate the establishment and stabilization of the primed state of acrosomal exocytosis that develops during the course of sperm capacitation. Additionally, we will examine the roles of intracelular calcium and actin in the destabilization of the primed state of acrosomal exocytosis that results in the propagation of the fusion of the outer acrosomal and plasma membranes. There are several human health-related reasons these studies are significant. For example, an understanding this process may lead to a better understanding of certain cases of male infertility and to the development of pharmacological approaches to interfere with this process, leading to new contraceptive agents. Most importantly, since actin has been implicated in exocytosis occurring in many types of somatic cells, information gathered from studying the less complicated sperm system will likely impact our understanding of secretion in other organ systems such as endocrine or digestive tissues.