Characterization of Endosomes in Development Intestine

超出所提供的空间。在肠的发育过程中，吸收细胞经历了一个阶段，在这个阶段，它们高度特化地从肠腔内吞下大分子。在这段时间内（取决于物种，可能发生在子宫内或出生后），这些细胞含有一个复杂的内体复合物。尽管该复合物已被证明在肠道和其他器官系统发育的关键生长因子的分选和选择性跨上皮运输中起重要作用，但对于允许这种选择性跨上皮运输的细胞机制知之甚少，而抗原和病原体被阻止使用相同的途径。为了确定选择性转运的机制，有必要描述内化大分子分选所涉及的隔室。我们将利用内管蛋白（一种发育中的肠的顶端内体蛋白）来确定在这个内体腔室中分选的分子机制。目前的研究目标是：1)确定参与根尖内体蛋白分选的分子；2)确定磷酸化在内噬作用和内管素循环中的作用；3)分析内管素表达中断对肠细胞发育的影响。这项内体结构和调控的研究将提供对上皮细胞功能和上皮极性维持重要的分子机制的见解。从长远来看，这些研究将深入了解发育重要配体（如生长因子）的分选和靶向机制。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。了解选择性经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。网站性能 ======================================== 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===========================================