Functions of the Epithelial Septate Junction

上皮细胞的发育和功能中的一个中心问题是特化的过程 形成并维持膜结构域。这些区域，包括顶端和基底外侧 膜，连接复合体，和其他亚区，在组织和 划分与膜相关的功能。细胞间连接，包括粘连、紧密和 间隔连接，在细胞间黏附和防止细胞旁黏附方面具有明确的结构功能 流。此外，越来越多的证据表明，这些交汇点和其他专门的 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专门的膜域是如何 细胞间连接和信号复合体，在发育中的上皮细胞中被建立和调节。 更具体地说，我们计划阐明上皮间隔连接的功能，这是 果蝇上皮细胞之间形成的连接复合体。分隔的结在结构上和 与哺乳动物的结旁连接同源，它将Ranvier的结节与 轴突的有髓部分。我们实验室和其他实验室的研究已经确定了几个隔膜 但我们对其结构和功能的了解仍然非常有限。脱掉 就这些重要问题，我们计划： 1)利用遗传学和细胞学方法鉴定新的间隔连接成分。 2)研究Ankyrin的功能，Ankyrin是一种膜相关蛋白，被认为与一些 间隔连接成分，在组织基侧膜上。 3)研究隔连接和建立和 维持顶端/基底上皮的极性。 这些实验可望为所有至关重要的问题提供洞察。 发育中的组织，特别是上皮。了解更多关于上皮细胞 建立和保持联系，调节细胞旁扩散，并形成专门的膜域 不仅对理解正常的生理和发育很重要，而且对阐明过程也很重要。 与多种人类疾病有关。

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.