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.

项目摘要/摘要 哺乳动物卵母细胞成熟的调节是形成的核心 可以施肥并发展成可行的胚胎的成熟卵。卵母细胞成熟 包括通过减数分裂将核材料划分以形成单倍体卵细胞，因为 以及允许卵子激活的细胞结构和信号通路的变化 通过受精和随后发育的精子。未成熟的集合 人类辅助生殖诊所中的卵母细胞仍然很普遍，并且更大 需要了解以确保在临床环境中获得成熟的卵。 此外，减数分裂过程中纺锤体的异常可能与 具有非整倍性的发生率。该提议的目的是提供有关 以后可以应用于动物和人类的基本细胞机制 生殖。指导卵母细胞成熟和减数分裂纺锤的细胞途径 减数分裂过程中的功能很复杂，并且取决于复杂的相互作用 和蛋白质组合之间。研究此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）蛋白是许多信号中的重要调节剂 转导途径，细胞周期控制，蛋白质运输，凋亡以及 胚胎发展。有证据表明14-3-3蛋白也是 减数分裂和减数分裂纺锤体的关键调节剂。总体目标 该项目是描述14-3-3蛋白在卵母细胞成熟中的功能。专注 在理解哺乳动物卵母细胞成熟和 早期发展，在目标1和2中，将通过检查14-3-3的作用。 七个14-3-3同工型形成二聚体并详细介绍蛋白质 它们参与的复合物。卵母细胞特异性的14-3-3敲除鼠标模型将是 在AIM 3中用于检验14-3-3蛋白有助于调节的假设 减数分裂和主轴形成。识别相互作用蛋白质和 确定这种互动的功能将增强我们对 哺乳动物的卵子。