Signaling Mechanisms of Polyspermy Block

多精阻断的信号机制

• 批准号: 8920664
• 负责人: Anne E Carlson
• 金额: $ 23.84万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8920664
• 关键词: Affect; African; Anions; Biological Models; Biology; Biophysics; Caliber; Cells; Child Mortality; Chromosome abnormality; Contraceptive methods; Diagnosis; Dominant-Negative Mutation; Economics; Electrophysiology (science); Embryo; Embryonic Development; Ensure; Event; Family Planning; Fertilization; Future; Genes; Genetic Transcription; Goals; Image; Infant Mortality; Infertility; Ion Channel; Left; Life; Maternal Mortality; Mediating; Membrane; Methods; Molecular; Nature; Organism; Permeability; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Play; Process; RNA Interference; Rana; Reproduction; Reproductive Biology; Reproductive Medicine; Role; Signal Pathway; Signal Transduction; Source; Spontaneous abortion; Staging; Techniques; Testing; Time; Training; Water; Woman; Xenopus laevis; Xenopus sp.; abstracting; base; cost effective; egg; human genome sequencing; meetings; mortality; novel; prevent; protein expression; research study; sperm cell; tool

Project Summary/Abstract: Fertilization is one of the most fundamental processes in nature, yet critical gaps exist in our understanding of this essential process. One of the earliest and most prevalent barriers to successful reproduction is the fertilization of an egg by more than one sperm, or polyspermy. This common problem, faced by the eggs of all sexually reproducing species, causes severe chromosomal defects and leads to embryonic mortality. This project will investigate the molecular mechanisms that ensure that each egg is fertilized by only one sperm, thus allowing for normal embryonic development. In the eggs of many organisms, fertilization evokes a prolonged membrane depolarization, which acts as a fast block to polyspermy. The fast polyspermy block requires the activity of one of more ion channel, but the molecular identity of any required channel is not known. In many species, including frogs, Cl- channels likely mediates this process. Coincidentally, a fertilization-induced increase in Ca2+ also occurs prior to the fast polyspermy block. A possible connection between these two events is the recently identified Ca2+- activated Cl- channel encoded by the TMEM16a gene. In specific aim one, I will identify the source of Ca2+ required for the depolarization at fertilization. Experiments outlined in specific aim two will uncover the role of the TMEM16a channel in the fast polyspermy block. Along with a fertilization-evoked increase in Ca2+, fertilization is also accompanied by a two-fold increase in phosphatidylinositol 4,5-bisphosphate (PIP2). The role that this elevated PIP2 may play in the first minutes after fertilization is unknown. Because PIP2 is a known regulator of structurally diverse ion channels and because the fertilization- evoked PIP2 elevation occurs within the time frame of the fast polyspermy block, I hypothesize that PIP2 regulates the fertilization-evoked depolarization. I will test this hypothesis in specific aim three and determine if PIP2 depletion affects the polyspermy block. The results of these experiments will contribute to our understanding of the biology of fertilization, and will provide the basis for future advances is reproductive medicine.

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