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

项目总结/摘要 哺乳动物卵母细胞成熟的调节是形成 能够受精并发育成可存活胚胎的成熟卵子。卵母细胞成熟 包括通过减数分裂分裂核物质以形成单倍体卵细胞，如 以及细胞结构和信号通路的变化， 精子在受精和随后的发育过程中产生的。不成熟的收藏 人类辅助生殖诊所中的卵母细胞仍然很常见， 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 非整倍体的发生率。本建议的目的是提供深入了解 基本的细胞机制，以后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，并依赖于复杂的相互作用， 和蛋白质组合之间的关系。研究这一过程的一种方法是检查 关键衔接子和调节蛋白的作用及其与已知信号传导的相互作用 这些因子，特别是我们所知的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）蛋白是许多信号转导的重要调节因子， 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蛋白也是 减数分裂和减数分裂纺锤体形成中的关键调节因子。的总目标 本课题旨在研究14-3-3蛋白在卵母细胞成熟过程中的作用。聚焦 填补了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的早期开发中，将通过检查 七种14-3-3异构体中的每一种，因为它们形成二聚体并详细描述了蛋白质 他们参与的复杂。卵母细胞特异性14-3-3基因敲除小鼠模型将在 在目的3中使用，以检验14-3-3蛋白有助于调节 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 哺乳动物卵子发生

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.