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）：上皮细胞发育和功能的核心问题是形成和维持特化膜域的过程。这些结构域，包括顶膜和基底外侧膜、连接复合体和其他子结构域，对于组织和划分膜相关功能非常重要。细胞间连接，包括粘附连接、紧密连接和隔膜连接，在细胞间粘附和防止细胞旁流中具有明确的结构功能。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发挥着重要作用。该提案的总体目标是更好地了解特殊的膜结构域（包括细胞间连接和信号复合物）在发育中的上皮细胞中是如何建立和调节的。更具体地说，我们计划阐明上皮隔膜连接的功能，上皮隔膜连接是果蝇上皮细胞之间形成的连接复合体的关键部分。隔膜连接在结构和分子上与哺乳动物的节点旁连接同源，该连接将朗飞节与轴突的有髓鞘部分分开。我们实验室和其他实验室的研究已经确定了一些隔膜连接成分，但我们对其结构或功能的了解仍然非常有限。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隔膜连接成分。 2) 研究锚蛋白（一种膜相关蛋白，据信与一些隔膜连接成分相互作用）在组织基底外侧膜中的功能。 3) 检查隔膜连接处和建立和维持顶端/基底上皮极性的机制之间的功能相互作用。这些实验有望为所有发育组织，特别是上皮细胞中的根本性重要问题提供见解。更多地了解上皮细胞建立和维持接触、调节细胞旁扩散和形成专门的膜域的机制不仅对于理解正常生理和发育很重要，而且对于阐明与各种人类疾病相关的过程也很重要。