Characterization of Endosomes in Development Intestine

超出所提供的空间。 在肠道发育过程中，吸收细胞会经历一个高度专门化从肠腔内吞大分子的阶段。在此期间（根据物种的不同，可能发生在子宫内或出生后），这些细胞含有复杂的内体复合物。尽管这种复合物已被证明在生长因子的分类和选择性跨上皮运输中非常重要，而生长因子对于肠道和其他器官系统的发育至关重要，但人们对允许这种选择性跨上皮运输同时防止抗原和病原体利用相同途径的细胞机制知之甚少。为了确定选择性转运的机制，有必要表征参与内化大分子分类的区室。我们将利用内管蛋白（发育中肠道的顶端内体蛋白）来定义参与该内体区室分选的分子机制。当前提案的目标是 1) 识别参与顶端内体蛋白分选的分子，2) 定义磷酸化在内管蛋白的内吞作用和再循环中的作用，3) 分析内管蛋白表达破坏对肠上皮细胞发育的影响。对内体结构和调节的研究将深入了解对上皮细胞功能和上皮极性维持重要的分子机制。从长远来看，这些研究将深入了解生长因子等发育重要配体的分类和靶向机制。此外，由于上皮细胞选择性排除抗原或病原体的能力对于正常功能也至关重要，因此了解这一过程的机制至关重要。了解选择性跨上皮转运的机制将增强我们对肠道屏障的理解，并为预防机会性感染和不适当的抗原转运提供策略。表演网站==========================================章节结束==============================================

EXCEED THE SPACE PROVIDED. During the development of the intestine, the absorptive cells go through a stage in which they arehighly specialized for endocytosis of macromolecules from the intestinal lumen. During this time (which, depending upon the species, may occur in utero or after birth) these cells contain an elaborate endosomal complex. Although this complex has been shown to be important in the sorting and selective transepithelial transport of growth factors that are critical for the development of the intestine and other organ systems, little is known about the cellular mechanisms that allow for this selective transepithelial transport while antigens and pathogens are prevented from utilizing the same route. To identify the mechanisms that underlie selective transport, it is necessary to characterize the compartment involved in sorting of internalized macromolecules. We will utilize endotubin, an apical endosomal protein of the developing intestine, to define the molecular machinery involved in sorting in this endosomal compartment. The goals of the current proposal are to 1) identify molecules involved in sorting of apical endosomal proteins, 2) define the role of phosphorylation in the endocytosis and recycling of endotubin, 3) analyze the effect of disruption of endotubin expression on enterocyte development. This investigation of endosomal structure and regulation will provide insight into the molecular machinery important for epithelial cell function and the maintenance of epithelial polarity. In the long term, these studies will provide insight into the mechanism of sorting and targeting of developmentally important ligands such as growth factors. In addition, since the ability of the epithelial cells to selectively exclude antigens or pathogens is also critical to normal function, it is crucial that we understand the mechanisms of this process. Understanding the mechanisms of selective transepithelial transport will enhance our understanding of the intestinal barrier and provide strategies for the prevention of opportunistic infection and inappropriate antigen transport. PERFORMANCE SITE ========================================Section End===========================================