Mechanism and function of a novel actin nucleator

新型肌动蛋白成核剂的机制和功能

• 批准号: 7382536
• 负责人: R DYCHE MULLINS
• 金额: $ 25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382536
• 关键词: Actins; Adult; Affinity; Anterior; Architecture; Binding; Biochemical; Brain; Cell Nucleus; Cell physiology; Class; Complex; Coupled; Development; Dorsal; Drosophila genus; Electron Microscopy; Embryo; End Point; Eukaryotic Cell; Family; Filament; Genes; Genetic; Goals; Golgi Apparatus; Human; In Vitro; Intracellular Transport; Lipid Binding; Lipids; Localized; Mammals; Mediating; Membrane; Microfilaments; Molecular; Neurons; Oocytes; Organism; Pathway interactions; Pattern; Personal Satisfaction; Phenotype; Play; Protein Family; Proteins; Regulation; Reporting; Research Personnel; Role; Shapes; Specificity; Structure; Tissues; To specify; Variant; Work; cell type; dimer; in vivo; interest; member; monomer; mutant; novel; particle; programs; reconstruction; stoichiometry; tissue/cell culture; tyrosine kinase ABL1

We recently showed that the product of the Drosophila spire gene, p150-Spir (Spir) nucleates actin filament formation by a unique mechanism (Quinlan et al.,2005). We recently discovered that Spir binds directly to members of another class of actin nucleators, the Cappuccino-family formins (Preliminary Results). This result is consistent with previous genetic studies indicating that the two proteins operate in the same pathway to specify both anterior-posterior and dorsal-ventral axes of developing embryos (Manseau and Schupach, 1989) and localization studies demonstrating that they have identical expression patterns in embryonic and adult mammalian tissues (Schumacher et al.,2004). Spir- and Cappuccino-family proteins are conserved across metazoan species from fruitflies to humans and in mammals and every organism known to express a Spir-family protein also expresses a Cappuccino-family formin. Despite their conservation and their importance in development, however, the function and regulation of Spir and Capu are not well understood. Our results suggest that the activities of Spir and Cappuccino are directly coupled and that they may function together in vivo as a single filament-forming complex. Our long-term goal is to understand how these actin nucleation factors work together to determine polarity of oocytes and embryos. Our short-term goals are to understand the activities of Spir and Capu alone and in complex. We will also investigate a potential mechanism by which the two proteins may be targeted in vivo. Specifically, we will: 1. Determine the mechanism of actin nucleation by Spir. 2. Characterize the interaction of Cappuccino with actin. 3. Characterize the interaction between Spir and Cappuccino. 4. Characterize the interaction of the Spir FYVE domain with lipids.

我们最近发现果蝇spire基因的产物p150-Spir（Spir）使肌动蛋白丝成核 通过独特的机制形成（Quinlan等人，2005年）。我们最近发现Spir直接与 另一类肌动蛋白成核剂的成员，卡布奇诺家族形成蛋白（初步结果）。这 这一结果与先前的遗传研究一致，表明这两种蛋白质在相同的基因组中起作用。 途径来指定发育胚胎的前后轴和背腹轴（曼索和 Schupach，1989）和定位研究，表明它们具有相同的表达模式， 胚胎和成年哺乳动物组织（Schumacher等，2004年）。Spir和Cappuccino家族蛋白 从果蝇到人类，从哺乳动物到所有生物， 已知表达Spir家族蛋白的人也表达Cappuccino家族蛋白。尽管他们 保护和发展的重要性，然而，Spir和Capu的功能和调节 并没有得到很好的理解。我们的研究结果表明，Spir和Cappuccino的活动是直接耦合的 并且它们可以在体内作为单一的致敏剂形成复合物一起起作用。我们的长期目标是 了解这些肌动蛋白成核因子如何共同作用以决定卵母细胞和胚胎的极性。 我们的短期目标是了解Spir和Capu的活动。我们还将 研究这两种蛋白质在体内靶向的潜在机制。具体而言，我们将： 1.用Spir确定肌动蛋白成核的机制。 2.描述卡布奇诺与肌动蛋白的相互作用。 3.描述Spir和Cappuccino之间的相互作用。 4.表征Spir FYVE结构域与脂质的相互作用。