The Role of 14-3-3 Proteins in Oogenesis and Early Development

14-3-3 蛋白在卵子发生和早期发育中的作用

• 批准号: 9170889
• 负责人: SRINIVASAN VIJAYARAGHAVAN
• 金额: $ 43.35万
• 依托单位: KENT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9170889
• 关键词: Adaptor Signaling Protein; Affect; Aneuploidy; Animals; Apoptosis; Binding; Binding Proteins; Biological Assay; Cdc25B protein; Cell Cycle Regulation; Cells; Cellular Structures; Clinic; Clinical; Collection; Complex; Cre-LoxP; Data; Development; Embryo; Embryonic Development; Ensure; Fertility; Fertilization; Fluorescence Microscopy; Gene Expression; Genes; Germ Cells; Goals; Haploidy; Heterodimerization; Homodimerization; Human; In Situ; In Vitro; Incidence; Infertility; Knock-out; Knockout Mice; Ligation; LoxP-flanked allele; Mammals; Meiosis; Meiotic Prophase I; Mus; Nature; Oocytes; Oogenesis; Ovary; Partner in relationship; Pathway interactions; Phenotype; Phosphoric Monoester Hydrolases; Phosphorylation; Phosphotransferases; Process; Production; Protein Isoforms; Proteins; Regulation; Reproduction; Research; Research Design; Role; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Somatic Cell; Structural Genes; System; Testing; Transgenic Mice; Variant; Work; abstracting; alpha Tubulin; assisted reproduction; dimer; egg; genetic regulatory protein; in vivo; insight; monomer; mouse model; nuclear division; oocyte maturation; promoter; protein complex; protein transport; recombinase; research study; sperm cell

Project Summary/Abstract The regulation of mammalian oocyte maturation is central to the formation of mature eggs that can be fertilized and develop into viable embryos. Oocyte maturation includes division of the nuclear material through meiosis to form a haploid egg cell, as well as changes in cell structure and signaling pathways that permit activation of the egg by sperm at fertilization and subsequent development. The collection of immature oocytes in human assisted reproduction clinics remains common, and greater understanding is needed to ensure the availability of mature eggs in clinical settings. Moreover, abnormalities of the spindle apparatus during meiosis could be associated with incidences of aneuploidy. The objective of this proposal is to provide insight into the basic cellular mechanisms that could later be applied to both animal and human reproduction. The cellular pathways that guide oocyte maturation and meiotic spindle function during meiosis are complex and are dependent on intricate interactions among and between protein assemblages. One approach to studying this process is to examine the role of key adaptor and regulatory proteins and their interaction with known signaling factors, particularly the kinases and phosphatases that we know to be central to meiosis. The 14-3-3 (YWHA) proteins in somatic cells are vital regulators in a number of signal transduction pathways, cell cycle control, protein trafficking, apoptosis, and aspects of embryonic development. There is evidence to indicate that the 14-3-3 proteins are also critical regulators in meiosis and in the formation of meiotic spindles. The overall goal of this project is to delineate the functions of 14-3-3 proteins in oocyte maturation. Focusing on filling in some of the gaps in our understanding of mammalian oocyte maturation and early development, in Aims 1 and 2, the role of 14-3-3 will be assessed by examining each of the seven 14-3-3 isoforms as they form dimers and detailing the protein complexes they are involved in. Oocyte-specific 14-3-3 knockout mouse models will be used in Aim 3 to test the hypothesis that 14-3-3 proteins contribute to the regulation of meiosis and spindle formation. The combination of identifying interacting proteins and determining the function of such interactions will enhance our understanding of mammalian oogenesis.

项目概要/摘要 哺乳动物卵母细胞成熟的调节对于卵母细胞的形成至关重要 成熟的卵子可以受精并发育成可存活的胚胎。卵母细胞成熟 包括核物质通过减数分裂分裂形成单倍体卵细胞，如 以及允许卵子激活的细胞结构和信号通路的变化 由精子在受精和随后的发育过程中产生。不成熟的集合 人类辅助生殖诊所中的卵母细胞仍然很常见，而且更多 需要了解以确保临床环境中成熟卵子的可用性。 此外，减数分裂期间纺锤体的异常可能与 与非整倍体的发生率有关。该提案的目的是提供对 基本的细胞机制后来可以应用于动物和人类 生殖。指导卵母细胞成熟和减数分裂纺锤体的细胞途径 减数分裂过程中的功能是复杂的，并且依赖于之间复杂的相互作用 以及蛋白质组合之间。研究这个过程的一种方法是检查 关键适配器和调节蛋白的作用及其与已知信号传导的相互作用 因素，特别是我们知道对减数分裂至关重要的激酶和磷酸酶。 体细胞中的 14-3-3 (YWHA) 蛋白是许多信号的重要调节因子 转导途径、细胞周期控制、蛋白质运输、细胞凋亡以及 胚胎发育。有证据表明 14-3-3 蛋白也 减数分裂和减数分裂纺锤体形成的关键调节因子。总体目标为 该项目旨在描述 14-3-3 蛋白在卵母细胞成熟中的功能。聚焦 填补我们对哺乳动物卵母细胞成熟理解的一些空白 在目标 1 和 2 的早期发展中，将通过检查来评估 14-3-3 的作用 七个 14-3-3 同工型中的每一个形成二聚体并详细说明蛋白质 卵母细胞特异性 14-3-3 敲除小鼠模型将 用于目标 3 来检验 14-3-3 蛋白有助于调节的假设 减数分裂和纺锤体形成。识别相互作用的蛋白质和 确定这种相互作用的功能将增强我们对 哺乳动物的卵子发生。