Characterization of Endosomes in Development Intestine

发育肠中内体的表征

• 批准号: 7053575
• 负责人: Jean M Wilson
• 金额: $ 4.4万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7053575
• 关键词: biomarker; endocytosis; gastrointestinal absorption /transport; gastrointestinal epithelium; glycoprotein structure; glycoproteins; growth /development; immunocytochemistry; immunoelectron microscopy; intracellular membranes; intracellular transport; laboratory rat; membrane structure; molecular cloning; newborn animals; nucleic acid probes; protein sequence; tissue /cell culture; transfection; vesicle /vacuole

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

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高度特化的阶段，用于从肠腔中内吞大分子。在此期间（取决于物种，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。虽然这种复合物已被证明是重要的生长因子的分选和选择性transepithelial运输是至关重要的肠和其他器官系统的发展，很少有人知道的细胞机制，允许这种选择性transepithelial运输，而抗原和病原体被阻止利用相同的途径。要确定的机制，选择性运输的基础上，它是必要的，以表征参与排序的内化大分子的隔室。我们将利用内管蛋白，顶端的内体蛋白的发展肠，定义的分子机制，在这个内体区室参与排序。目前的建议的目标是1）确定参与顶端内体蛋白分选的分子，2）确定磷酸化在内吞作用和内管蛋白再循环中的作用，3）分析内管蛋白表达中断对肠上皮细胞发育的影响。内体结构和调节的研究将提供深入了解上皮细胞功能和维持上皮极性的重要分子机制。从长远来看，这些研究将提供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，因此我们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。性能现场=