ROLE OF ACTIN CYTOSKELETON DURING MOUSE SPERM ACROSOMAL EXOCYTOSIS

肌动蛋白细胞骨架在小鼠精子顶体胞吐作用中的作用

• 批准号: 8626253
• 负责人: Mariano G Buffone
• 金额: $ 5.18万
• 依托单位: FUND INST BIOL Y MED EXPERIMENTAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-09 至 2016-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8626253
• 关键词: Acrosome; Actins; Biochemical; Calcium; Cell membrane; Cells; Contraceptive Agents; Cytoskeleton; Data; Development; Docking; Endocrine; Epididymis; Event; Exhibits; Exocytosis; F-Actin; Female; Fertilization; G Actin; Goals; Golgi Apparatus; Health; Herpes zoster disease; Human; Investigation; Laboratories; Lead; Left; Male Infertility; Mammalian Cell; Mammals; Membrane; Membrane Fusion; Methods; Molecular; Mus; Nuclear Envelope; Organelles; Particulate; Physiological; Play; Process; Progesterone; Publishing; Reaction; Research; Resolution; Role; Series; Signal Pathway; Signal Transduction; Somatic Cell; Sperm Capacitation; Sperm Head; Spermatogenesis; Staging; Stimulus; Swimming; System; Testing; Time; Tissues; Vesicle; Zona Pellucida; base; body system; cell motility; depolymerization; egg; information gathering; polymerization; reproductive; research study; response; sperm cell; zygote

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.

概括 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。 获能通过启动细胞经历快速胞吐事件而使精子具有能力 称为顶体胞吐作用，由卵子透明带 (ZP) 或黄体酮刺激。 多年来，一些生化事件与获能过程有关。 然而，在获能研究中仍未得到解答的问题是： 将精子细胞从对 ZP 无反应的状态转变为潜在的反应或一组反应，或 黄体酮刺激顶体胞吐作用到准备对这些刺激做出反应的状态吗？我们的 初步结果表明肌动蛋白细胞骨架在此过程中发挥作用。我们的长期 本研究的目标：阐明肌动蛋白细胞骨架控制的分子机制 哺乳动物精子顶体胞吐作用。在本提案中，我们评估了建立和 精子过程中形成的顶体胞吐作用的启动状态的稳定 获能。此外，我们将研究细胞内钙和肌动蛋白在 顶体胞吐作用的引发状态不稳定，导致融合的传播 外部顶体膜和质膜。有几个与人类健康相关的原因 研究意义重大。例如，理解这个过程可能会导致更好的理解 某些男性不育病例的研究以及干扰药理学方法的开发 通过这个过程，产生了新的避孕药。最重要的是，由于肌动蛋白已被牵连 在许多类型的体细胞中发生的胞吐作用中，通过研究较少的细胞收集的信息 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，例如 如内分泌或消化组织。