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: 8440698
• 负责人: Mariano G Buffone
• 金额: $ 5.08万
• 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/8440698
• 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.

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