Cytoskeletal mechanisms of oocyte polarity

卵母细胞极性的细胞骨架机制

• 批准号: 9362068
• 负责人: Vladimir I Gelfand
• 金额: $ 31.01万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9362068
• 关键词: Actin-Binding Protein; Actins; Address; Animal Model; Anterior; Binding; Binding Proteins; Birth; Blood Circulation; Cell Polarity; Cells; Cytoplasm; Cytoplasmic streaming; Cytoskeleton; Data; Destinations; Development; Development Polarity; Drosophila genus; Drosophila melanogaster; Embryo; Embryonic Development; F-Actin; Generations; Genetic; Goals; Grant; Human; Human body; Image; Imaging Device; Impairment; Individual; Injectable; Interphase Cell; Kinesin; Knowledge; Light; Maintenance; Microfilaments; Microtubules; Modeling; Molecular; Molecular Motors; Motor; Movement; Myosin Type V; Neurodegenerative Disorders; Nurses; Oocytes; Oogenesis; Ovary; Pattern; Process; Proteins; Publications; Publishing; RNA; RNA-Binding Proteins; Role; Site; Slide; Stream; System; Testing; Transport Process; Tropomyosin; Work; base; experimental study; high resolution imaging; link protein; mutant; new therapeutic target; novel; particle; tool

Abstract The goal of this grant is to study how microtubules, actin filaments, and motor proteins generate polarity in Drosophila oocytes. Oocyte polarity is critical for early embryonic development, and polarity determinants are conserved between Drosophila and humans, allowing us to study polarity determination using a genetic system amenable to high-resolution imaging. We will use live imaging to study molecular mechanisms of transport and posterior oocyte anchoring of an evolutionary conserved polarity determinant Staufen. We will test a hypothesis that Staufen is transported in the nurse cells of Drosophila ovaries and between individual cells through the ring canals in the form attached to microtubules, and that these microtubules are moved in the cytoplasm and through the ring canals by molecular motors. We will identify these motors and find the proteins that attach Staufen to microtubules. Our lab has discovered that conventional kinesin has a new and conserved function of sliding microtubules against each other and generated new genetic tools that allow us to microtubule-sliding and cargo-transporting functions of kinesin. Using these tools, we will determine the role of microtubule-microtubule sliding in kinesin localization. We will explore the role of the cortical network of actin filaments in the localization of Staufen and will test the hypothesis that competition between cortical anchoring to actin and transport by or along microtubules defines the final asymmetrical distribution of Staufen. We will identify proteins that link Staufen with the posterior cortex in the oocyte. This work will advance our knowledge of fundamental transport processes that define cell polarity, and early embryonic development.

抽象的 该赠款的目的是研究微管，肌动蛋白丝和运动蛋白如何在 果蝇卵母细胞。卵母细胞极性对于早期胚胎发育至关重要，极性决定因素是 果蝇和人之间的保守，使我们能够使用遗传系统研究极性测定 适合高分辨率成像。我们将使用实时成像研究运输的分子机制和 进化保守的极性决定因素Staufen的后卵母细胞锚定。我们将测试 假设Staufen在果蝇卵巢的护士细胞和单个细胞之间运输 通过附着在微管上的形式的环管，这些微管在 细胞质和通过分子电动机通过环管。我们将识别这些电机并找到蛋白质 那将Staufen连接到微管上。我们的实验室发现，常规动力蛋白有一个新的和 滑动微管相互对立的保守功能，并生成了新的遗传工具，使我们能够 驱动蛋白的微管滑动和货物运输功能。使用这些工具，我们将确定 微管微管在驱动蛋白定位中滑动。我们将探讨肌动蛋白皮质网络的作用 Staufen定位的细丝，并将检验以下假设，即皮质锚定竞争 通过微管或沿微管进行肌动蛋白和运输定义了Staufen的最终不对称分布。我们将 鉴定将Staufen与卵母细胞中的后皮质联系起来的蛋白质。这项工作将提高我们的知识 定义细胞极性和早期胚胎发育的基本运输过程。