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: 8210119
• 负责人: Mariano G Buffone
• 金额: $ 5.35万
• 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 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8210119
• 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

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: In this application, we will contribute to elucidate the molecular mechanism whereby the actin cytoskeleton controls acrosomal exocytosis in mammalian sperm. Investigating acrosomal exocytosis may lead to better approaches to certain cases of male infertility and to the development of new contraceptive agents. Information gathered from studying the sperm system will impact our understanding of secretion in other organ systems such as endocrine or digestive tissues.

描述（由申请人提供）：哺乳动物的精子必须经历称为电容的过程才能有能力施肥卵。电容通过启动细胞进行启动的精子，以经历一个称为Arocomal cropytosis的快速胞吐事件，该事件由卵或孕酮的Zona Pelucida（ZP）刺激。多年来，几个生化事件与电容过程有关。但是，在对电容的研究中仍未得到答复的问题是：什么是基本反应或一组反应，将精子细胞从状态不反应转化为ZP或孕激素刺激的Arosomal盘问到该州的状态是什么？我们的初步结果表明，肌动蛋白细胞骨架在此过程中起作用。我们的这项研究的长期目标：阐明肌动蛋白细胞骨架控制哺乳动物精子中的蛇形胞吐作用的分子机制。在该提案中，我们评估了在精子电容过程中发育的杂色胞吞作用的启动状态的建立和稳定。此外，我们将研究细胞内钙和肌动蛋白在邻域胞胞菌病的启动状态下的稳定中的作用，从而导致外顶杂色体和质膜的融合传播。这些研究很重要，与人类健康相关的原因有几个。例如，理解这一过程可能会更好地理解某些男性不育症病例，并开发出干扰这一过程的药理学方法，从而导致新的避孕药。最重要的是，由于肌动蛋白与许多类型的体细胞中发生的胞吐作用有关，因此从研究较不复杂的精子系统中收集的信息可能会影响我们对其他器官系统（例如内分泌或消化组织）的分泌的理解。 公共卫生相关性：在此应用中，我们将有助于阐明肌动蛋白细胞骨架控制哺乳动物精子中的杂色胞吐作用的分子机制。调查脊髓囊肿的胞吐作用可能会导致某些男性不育症病例和新避孕药的发展提供更好的方法。从研究精子系统中收集的信息将影响我们对其他器官系统（例如内分泌组织或消化组织）的分泌的理解。