ROLE OF ACTIN CYTOSKELETON DURING MOUSE SPERM ACROSOMAL EXOCYTOSIS

总结 哺乳动物的精子必须经过一个被称为获能的过程才能使卵子受精。 获能通过使细胞经历快速胞吐事件而使精子有能力 被称为顶体胞吐作用，由卵细胞的透明质酸（ZP）或孕酮刺激。 多年来，一些生化事件已与获能过程; 然而，在对能力培养的研究中仍然没有回答的问题是： 使精子从对ZP无反应的状态转变的潜在反应或一组反应，或 胆固醇刺激的顶体胞吐反应到对这些刺激有反应的状态？我们 初步结果表明，肌动蛋白细胞骨架在这一过程中发挥作用。我们的长期 本研究的目的：阐明肌动蛋白细胞骨架控制细胞凋亡的分子机制， 哺乳动物精子的顶体胞吐作用。在本建议书中，我们评估了建立和 稳定精子过程中发生的顶体胞吐作用的启动状态 获能此外，我们还将研究细胞内钙离子和肌动蛋白在细胞凋亡中的作用。 顶体胞吐作用引发状态的不稳定，导致融合的增殖， 外顶体膜和质膜。有几个与人类健康有关的原因， 研究意义重大。例如，理解这个过程可能会导致更好地理解 某些男性不育症的病例，并开发药物方法来干预 通过这个过程，产生了新的避孕药。最重要的是，由于肌动蛋白与 在许多类型的体细胞中发生的胞吐作用中，从研究较少的 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.