Characterization of Endosomes in Development Intestine

超出提供的空间。在肠道的发育过程中，吸收细胞经历了一个阶段，在这个阶段，它们高度专门化地内吞来自肠腔的大分子。在这段时间(根据物种的不同，可能发生在子宫内或出生后)，这些细胞包含一个精心制作的内体复合体。尽管这种复合体已被证明在对肠道和其他器官系统的发育至关重要的生长因子的分选和选择性跨上皮运输中起重要作用，但对允许这种选择性跨上皮运输的细胞机制知之甚少，同时阻止抗原和病原体利用相同的途径。为了确定选择性转运的机制，有必要确定内化大分子分选所涉及的隔室的特征。我们将利用内管素，一种发育中的肠道顶端内体蛋白，来确定在这个内体隔室中参与分选的分子机制。本研究的目标是：1)确定与顶端内体蛋白分选有关的分子；2)确定磷酸化在内吞作用和内管酶循环中的作用；3)分析内管酶表达中断对肠细胞发育的影响。这种对内体结构和调节的研究将提供对上皮细胞功能和维持上皮极性重要的分子机制的洞察力。从长远来看，这些研究将提供对生长因子等发育重要配体的分类和靶向机制的洞察力。此外，由于上皮细胞选择性地排除抗原或病原体的能力对正常功能也是至关重要的，因此我们理解这一过程的机制是至关重要的。了解选择性跨上皮转运的机制将加深我们对肠道屏障的了解，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========================================Section End===========================================

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===========================================