GPI-ANCHORED PROTEIN TRAFFICKING AND SIGNAL TRANSDUCTION

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 内吞运输是多种细胞功能的关键。在配体结合后，细胞表面受体的内化和细胞内行程对于它们调节多种关键过程的能力是至关重要的，包括营养摄取、细胞粘附、细胞迁移和受体信号传导。内化主要以依赖于网格蛋白和AP-2接头复合物的方式发生。然而，越来越多的受体被报道以不依赖网格蛋白的方式内化。这些受体的一个子集被称为糖基磷脂酰肌醇（GPI）锚定蛋白（GPI-AP），这是一个经过翻译后修饰将其共价连接到GPI的不同蛋白质家族。GPI-AP缺乏胞质尾，在富含胆固醇和鞘脂的膜内组织，并且这些区域由于其在生化梯度分级中的浮力而被称为“筏”。在这里，我们假设新发现的C-末端Eps 15同源结构域（EHD）蛋白在GPI-AP运输中起着关键作用。我们提供了令人信服的初步证据EHD 1在GPI-AP从早期内体运输到内吞再循环室的新功能，并解决GPI-AP内吞调节发生的机制。由于GPI-AP对补体反应、寄生虫进入和细胞迁移等多种细胞过程至关重要，因此加强对GPI-AP贩运的了解至关重要。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Endocytic trafficking is key to multiple cellular functions. Upon ligand binding, the internalization and intracellular itineraries of cell surface receptors is critical to their ability to regulate a wide variety of critical processes, including nutrient uptake, cell adhesion, cell migration, and receptor signaling. Internalization occurs mostly in a manner dependent upon clathrin and the AP-2 adaptor complex. However, a growing list of receptors has been reported to internalize in a clathrin-independent manner. One subset of these receptors is known as Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs), a diverse family of proteins that undergoes a post-translational modification linking them covalently to the GPI. GPI-APs, which lack cytoplasmic tails, are organized within membranes that are enriched with cholesterol and sphingolipids, and these regions are known as "rafts", due to their buoyancy in biochemical gradient fractionations. Here, we hypothesize that the newly identified C-terminal Eps15 homology domain (EHD) proteins play critical roles in GPI-AP trafficking. We provide compelling preliminary evidence for a novel function of EHD1 in the transport of GPI-APs from early endosomes to the endocytic recycling compartment, and address the mechanisms by which regulation of GPI-AP endocytosis occurs. Since GPI-APs are critical for multiple cellular processes like complement reactions, parasite entry and cell migration, an enhanced understanding of GPI-AP trafficking is of critical importance.