RECOGNITION AND SORTING OF GLYCOPROTEINS

质膜的组成和功能是由一种 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 蛋白质类，不仅在生物合成过程中， 再分配过程，如内部化和再循环， 受体介导的内吞作用，转胞吞作用，或 激素受体的下调。 疾病可能是由于 这些过程中的任何一个失败，或从它的使用颠覆 被病原体如病毒感染 本报告所述工作的重点 应用是确定高尔基体后分选的分子细节 事件 通过建立一些分类事件的细节，嗯- 已知的蛋白质如流感病毒血凝素和 多免疫球蛋白受体，我们打算提供的基础， 其他细胞类型中发生的分选事件的比较 涉及其他蛋白质。 一旦排序之间的关系 不同的蛋白质在不同的细胞类型被理解，它可能是 可以将这些信息用于诊断目的。研究 可以使用容易从人类患者分离的细胞类型的体外培养 以了解活检材料所对应的器官中的疾病过程， 限制性的，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： 跨膜蛋白包含分级的分选信号， 它们将被运送到不同的目的地， 不同的细胞类型 我们将研究潜在的根尖分选 许多蛋白质的跨膜片段中的信息， 建立这种类型的共有序列的目的是， 分选信号 我们建议鉴定与分选结合的蛋白质 信号，并确定富含鞘糖脂的 膜在流感病毒血凝素和其他 蛋白质被分选到上皮细胞或轴突的顶端表面， 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.