RECOGNITION AND SORTING OF GLYCOPROTEINS

质膜的组成和功能由一种 复杂的细胞内运输移动细胞表面糖蛋白之间 细胞器。这就需要对不同的数据进行识别和排序 蛋白质的种类，不仅在生物合成过程中，而且在 再分配过程，如内部化和再循环 受体介导的内吞、穿胞或 激素受体的下调。疾病可能是由 这些进程中的任何一个进程出现故障，或从其颠覆版本中使用 由病原体引起的，如病毒。本文件中所描述的工作重点 应用是确定高尔基体后分选的分子细节 事件。通过为几个人建立事件分类的细节，那么- 已了解的蛋白质如流感病毒血凝素和 多聚免疫球蛋白受体，我们打算提供一个基础 其他单元格类型中发生的排序事件的比较 涉及到其他蛋白质。一旦排序的关系与 不同细胞类型中的不同蛋白质被理解，它可能是 可以将此信息用于诊断目的。研究项目： 可以使用从人类患者中容易分离的细胞类型的体外实验 了解活组织检查材料所针对的器官的疾病过程 有限的，难以分离的，或难以维持的细胞 文化。 本申请中提出的实验将检验以下假设 跨膜蛋白包含分类信号的层次结构，从而允许 他们将被运输并本地化到不同的目的地 不同的细胞类型。我们将研究潜在的根尖排序 一些蛋白质跨膜片段中的信息 建立这种类型的共识序列的目的是 分拣信号。我们建议识别与分类相结合的蛋白质 信号和确定糖鞘糖脂富集化的作用 用于分离流感病毒血凝素等的膜 分选到上皮细胞或轴突顶面的蛋白质 神经元。

The composition and function of the plasma membrane is maintained by a complex intracellular traffic moving cell surface glycoproteins between organelles. This requires the recognition and sorting of different classes of proteins, not only during biosynthesis, but also during redistributive processes, such as the internalization and recycling of receptors during receptor-mediated endocytosis, transcytosis, or during the down-regulation of hormone receptors. Disease can result from the failure of any one of these processes, or from its subversion for use by a pathogen such as a virus. The focus of the work described in this application is to determine the molecular details of post-Golgi sorting events. By establishing the details of sorting events for a few, well- understood proteins such as the influenza virus hemagglutinin and polyimmunoglobulin receptor, we intend to provide the basis for a comparison of the sorting events that occur in other cell types involving other proteins. Once the relationship between the sorting of different proteins in different cell types is understood, it may be possible to use this information for diagnostic purposes. Studies in vitro of cell types easily isolated from human patients might be used to learn about disease processes in organs for which biopsy material is limiting, difficult to isolate, or the cells difficult to maintain in culture. Experiments proposed in this application will test the hypothesis that transmembrane proteins contain hierarchies of sorting signals that allow them to be transported and localized to different destinations in different cell types. We will investigate potential apical sorting information in the transmembrane segments of a number of proteins for the purpose of establishing a consensus sequence for this type of sorting signal. We propose to identify proteins that bind to sorting signals and to determine the role of glycosphingolipid-enriched membranes in the sorting of the influenza virus hemagglutinin and other proteins sorted to the apical surface of epithelial cells or axons of neurons.