Functions of the Epithelial Septate Junction

上皮隔膜连接处的功能

• 批准号: 7031954
• 负责人: Richard G Fehon
• 金额: $ 28.34万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7031954
• 关键词: Drosophilidae; RNA interference; ankyrins; apical membrane; arthropod genetics; basolateral membrane; cell component structure /function; cellular polarity; epithelium; gene expression; gene interaction; gene mutation; genetic regulation; genetic screening; guinea pigs; intermolecular interaction; laboratory mouse; laboratory rabbit; laboratory rat; membrane activity; membrane biogenesis; membrane structure; molecular assembly /self assembly; protein localization; protein structure function; transfection

DESCRIPTION (provided by applicant): A central problem in the development and function of epithelial cells is the process by which specialized membrane domains are formed and maintained. These domains, including the apical and basolateral membranes, the junctional complex, and other subdomains, are important in organizing and compartmentalizing membrane-related functions. Intercellular junctions, including adherens, tight, and septate junctions, have well-defined structural functions in intercellular adhesion and preventing paracellular flow. In addition, there is an increasing body of evidence that these junctions, and other specialized membrane domains, play an essential role in regulating signaling pathways. The overall goal of this proposal is to better understand how specialized membrane domains, including intercellular junctions and signaling complexes, are established and regulated in developing epithelial cells. More specifically, we plan to elucidate the functions of the epithelial septate junction, a key part of the junctional complex that forms between Drosophila epithelial cells. Septate junctions are structurally and molecularly homologous to the mammalian paranodal junction that separates the node of Ranvier from the myelinated portion of the axon. Studies in our laboratory and others have identified a handful of septate junction components, but we still have a very limited understanding of either its structure or function. To shed light on these important questions, we plan to: 1) Identify novel septate junction components using a genetic and cellular approaches. 2) Study the functions of Ankyrin, a membrane associated protein that is believed to interact with some septate junction components, in organizing the basolateral membrane. 3) Examine functional interactions between the septate junction and mechanisms that establish and maintain apical/basal epithelial polarity. These experiments are expected to provide insights into questions of fundamental importance in all developing tissues and in particular epithelia. Knowing more about the mechanisms by which epithelial cells establish and maintain contacts, regulate paracellular diffusion, and form specialized membrane domains is important not only for understanding normal physiology and development, but also for elucidating processes associated with a variety of human diseases.

描述（由申请人提供）：上皮细胞的开发和功能中的一个核心问题是形成和维护专门的膜结构域的过程。这些结构域，包括顶部和基底外侧膜，连接络合物和其他子域，对于组织和分隔膜相关功能至关重要。细胞间连接（包括粘附，紧密和分隔连接）在细胞间粘附中具有明确的结构功能，并防止细胞旁流动。此外，越来越多的证据表明，这些连接和其他专门的膜结构域在调节信号通路中起着至关重要的作用。该提案的总体目标是更好地了解如何在发育中的上皮细胞中建立和调节专门的膜结构域，包括细胞间连接和信号传导复合物。更具体地说，我们计划阐明上皮分隔连接的功能，这是果蝇上皮细胞之间形成的连接络合物的关键部分。分隔连接在结构和分子上与哺乳动物的偏anodal结的结构同源，该连接将Ranvier的节点与轴突的髓鞘形成部分分开。我们实验室和其他人的研究已经确定了少数分隔连接组件，但是我们对其结构或功能的理解仍然非常有限。为了阐明这些重要问题，我们计划：1）使用遗传和细胞方法识别新型的分隔连接组件。 2）研究一种膜相关蛋白Ankyrin的功能，该蛋白被认为与某些分隔连接组件相互作用，在组织基底外侧膜中。 3）检查建立和维持顶端/基础上皮极性的分隔连接与机制之间的功能相互作用。这些实验有望提供有关在所有发展中，尤其是上皮细胞中基本重要性问题的见解。更多地了解上皮细胞建立和维持接触，调节细胞细胞扩散并形成专门的膜结构域的机制，不仅对于理解正常的生理学和发育，而且对于阐明与各种人类疾病相关的过程都很重要。