Functions of the Epithelial Septate Junction

上皮细胞的发育和功能的一个中心问题是特化的上皮细胞的分化过程。 形成并维持膜结构域。这些区域，包括顶侧和基底侧 膜，连接复合体和其他子域，在组织和 划分膜相关功能。细胞间连接，包括粘附、紧密和 分隔连接，在细胞间粘附和防止细胞旁粘附中具有明确的结构功能 流此外，有越来越多的证据表明，这些连接点和其他专门的 膜结构域在调节信号传导途径中起重要作用。 这项提案的总体目标是更好地了解如何专门的膜域，包括 细胞间连接和信号复合物在发育中的上皮细胞中建立和调节。 更具体地说，我们计划阐明上皮分隔连接的功能， 果蝇上皮细胞之间形成的连接复合体。隔膜连接在结构上和 分子同源的哺乳动物paranodal交界处，分开节点的兰维尔从 轴突的有髓鞘部分。我们实验室和其他实验室的研究已经确定了一些有隔膜的 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。摆脱 为了解决这些重要问题，我们计划： 1)使用遗传学和细胞学方法鉴定新的分隔连接成分。 2)研究Ankyrin的功能，Ankyrin是一种膜相关蛋白，被认为与一些 分隔连接组件，在组织基底外侧膜。 3)检查分隔连接和建立和 维持顶端/基底上皮极性。 这些实验预计将提供洞察问题的根本重要性， 发育中的组织，特别是上皮细胞。了解更多关于上皮细胞 建立和维持接触，调节细胞旁扩散，并形成专门的膜结构域， 这不仅对理解正常生理和发育很重要， 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.