GPI-ANCHORED PROTEIN TRAFFICKING AND SIGNAL TRANSDUCTION

GPI 锚定蛋白运输和信号转导

• 批准号: 8168391
• 负责人: Naava Naslavsky
• 金额: $ 27.62万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168391
• 关键词: Address; Biochemical; C-terminal; Cell Adhesion; Cell Surface Receptors; Cell physiology; Cholesterol; Clathrin; Complement; Complex; Computer Retrieval of Information on Scientific Projects Database; Cytoplasmic Tail; Early Endosome; Endocytosis; Fractionation; Funding; GPI Membrane Anchors; Glycosylphosphatidylinositols; Grant; Institution; Ligand Binding; Link; Membrane; Nutrient; Parasites; Play; Post-Translational Protein Processing; Process; Protein Family; Proteins; Reaction; Receptor Signaling; Recycling; Regulation; Reporting; Research; Research Personnel; Resources; Role; Signal Transduction; Source; Sphingolipids; TFAP2A gene; Tertiary Protein Structure; United States National Institutes of Health; cell motility; novel; protein transport; receptor; trafficking; uptake

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 内吞转运是多种细胞功能的关键。在与配体结合时，细胞表面受体的内化和胞内行程对于它们调节多种关键过程的能力至关重要，包括营养吸收、细胞黏附、细胞迁移和受体信号转导。内化主要以依赖于网状蛋白和AP-2接头复合体的方式发生。然而，越来越多的受体被报道以不依赖于网状蛋白的方式内化。这些受体的一个子集被称为糖基磷脂酰肌醇锚定蛋白(GPI-APs)，这是一个不同的蛋白质家族，经历翻译后修饰，将它们与GPI共价连接。没有细胞质尾巴的GPI-AP组织在富含胆固醇和鞘脂的膜内，这些区域因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Eps15同源结构域(EHD)蛋白在GPI-AP运输中发挥关键作用。我们提供了令人信服的初步证据，证明EHD1在将GPI-AP从早期内吞体内运输到内吞循环室中具有新的功能，并解决了调节GPI-AP内吞作用发生的机制。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运输的了解至关重要。