Functions of the Epithelial Septate Junction

描述（由申请人提供）：上皮细胞发育和功能的一个中心问题是形成和维持专门的膜结构域的过程。这些结构域，包括顶膜和基底侧膜、连接复合体和其他亚结构域，在组织和区室化膜相关功能中很重要。细胞间连接，包括粘附连接、紧密连接和分隔连接，在细胞间粘附和阻止细胞旁流动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起着至关重要的作用。这项提案的总体目标是更好地了解如何专门的膜结构域，包括细胞间连接和信号复合物，建立和调节上皮细胞的发展。更具体地说，我们计划阐明上皮分隔连接，果蝇上皮细胞之间形成的连接复合体的关键部分的功能。分隔连接在结构上和分子上与哺乳动物的Paranodal junction同源，Paranodal junction将Ranvier结与轴突的有髓部分分开。在我们的实验室和其他人的研究已经确定了少数分隔连接组件，但我们仍然有一个非常有限的了解，无论是其结构或功能。为了阐明这些重要问题，我们计划：1）使用遗传和细胞方法鉴定新的分隔连接组件。2)研究锚蛋白的功能，锚蛋白是一种膜相关蛋白，被认为与一些分隔连接组件相互作用，在组织基底外侧膜。3)检查隔膜连接和建立和维持顶端/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中的组织，特别是上皮细胞中具有根本重要性的问题提供见解。了解更多关于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结构域的机制不仅对理解正常生理和发育很重要，而且对阐明与各种人类疾病相关的过程也很重要。

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.