Characterization of pak kinase function in drosophila oogenesis

果蝇卵子发生中 pak 激酶功能的表征

• 批准号: 217532-2008
• 负责人: Harden, Nicholas
• 金额: $ 3.57万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=424945
• 关键词: Characterization; pak; kinase; function; drosophila

The Rho family of Ras-related small GTPases act as molecular switches, cycling between "on" and "off" states. They convey information into the cell and regulate cell shape and cell movement through proteins such as Pak. Epithelia are sheets of cells that include the skin and components of internal organs and are very important tissues in the development of animals. During the formation of epithelia, the Rho family and Pak help shape these tissues into their final configuration. Much of what is known about the Rho family and Pak has been come from studying cultured cells and relatively little is known about how these proteins operate in an intact organism. We are using the fruit fly Drosophila to genetically characterize the mechanisms by which Pak regulates epithelial development. Drosophila is a popular research organism due to the advanced techniques that have been developed for studying it, including very sophisticated genetic tools and the ability to do detailed imaging of events at the cellular level within the context of a whole animal. We have been looking at the follicular epithelium in the ovary, a typical epithelium that covers the developing egg. Using this system, we hope to gain insight into how Pak regulates three important processes in epithelial development. The first process is the regulation of cell adhesion, which is critical in determing how cells "stick" together to form tissues. The second is the regulation of epithelial cell shape through regulation of a contractile structure called the actomyosin cytoskeleton. Finally, we want to known how Pak regulates the proliferation of epithelial cells. Previous studies in other laboratories have identified various proteins regulating these three processes and we suspect that Pak interacts with these other poteins, perhaps by modifying their activity. We will use both genetics and biochemistry to address the relationship between Pak and these other regulators of epithelial development. This work will be of interest to developmental biologists and cell biologists, furthermore, improper development of epithelia is a cause of diverse birth defects, and our work may yield insight into what cell signaling pathways are defective in such disorders.

Ras相关的小GTP酶的Rho家族充当分子开关，在“开”和“关”状态之间循环。 它们将信息传递到细胞中，并通过Pak等蛋白质调节细胞形状和细胞运动。上皮是包括皮肤和内部器官的组成部分的细胞片，并且是动物发育中非常重要的组织。在上皮细胞的形成过程中，Rho家族和Pak帮助将这些组织塑造成其最终形态。关于Rho家族和Pak的大部分知识都来自于对培养细胞的研究，而关于这些蛋白质在完整生物体中如何运作的知识相对较少。我们正在使用果蝇的遗传特性的机制，Pak调节上皮细胞的发展。果蝇是一种受欢迎的研究生物体，因为已经开发了用于研究它的先进技术，包括非常复杂的遗传工具和在整个动物的背景下在细胞水平上对事件进行详细成像的能力。我们一直在观察卵巢中的滤泡上皮，这是一种典型的上皮，覆盖在发育中的卵子上。使用这个系统，我们希望深入了解Pak如何调节上皮发育中的三个重要过程。第一个过程是细胞粘附的调节，这对于决定细胞如何“粘”在一起形成组织至关重要。第二种是通过调节称为肌动球蛋白细胞骨架的收缩结构来调节上皮细胞的形状。最后，我们想知道Pak是如何调节上皮细胞增殖的。其他实验室的先前研究已经确定了调节这三个过程的各种蛋白质，我们怀疑Pak与这些其他potein相互作用，可能是通过改变它们的活性。我们将使用遗传学和生物化学来解决Pak和上皮发育的其他调节因子之间的关系。这项工作将是感兴趣的发育生物学家和细胞生物学家，此外，上皮细胞的发育不正常是多种出生缺陷的原因，我们的工作可能会产生洞察哪些细胞信号通路是有缺陷的，在这种疾病。