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.

摘要 这项资助的目标是研究微管、肌动蛋白细丝和马达蛋白是如何在 果蝇卵母细胞。卵母细胞的极性是早期胚胎发育的关键，而极性决定因素是 在果蝇和人类之间保守，使我们能够利用遗传系统研究极性决定 易于接受高分辨率成像。我们将使用实时成像来研究分子运输机制和 进化保守的极性决定簇Staufen的后卵母细胞锚定。我们将测试一个 斯陶芬在果蝇卵巢哺育细胞内和单个细胞之间转运的假说 以附着在微管上的形式穿过环状管道，这些微管在 细胞质，并通过分子马达通过环管。我们会鉴定这些马达并找到这些蛋白质 将史陶芬附着在微管上。我们的实验室发现，传统的激动素具有一种新的和 相互滑动的微管的保守功能，并产生了新的遗传工具，使我们能够 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-微管在运动蛋白定位中滑动。我们将探索肌动蛋白皮质网络的作用 细丝在Staufen的定位，并将检验皮质间竞争锚定的假说 肌动蛋白通过微管或沿微管运输决定了斯陶芬的最终不对称分布。我们会 识别连接Staufen和卵母细胞后皮质的蛋白质。这项工作将增进我们的知识 决定细胞极性的基本运输过程，以及早期胚胎发育。