GPI-ANCHORED PROTEIN TRAFFICKING AND SIGNAL TRANSDUCTION

GPI 锚定蛋白运输和信号转导

• 批准号: 8360442
• 负责人: Naava Naslavsky
• 金额: $ 27.19万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360442
• 关键词: Address; Biochemical; C-terminal; Cell Surface Receptors; Cell physiology; Cell-Cell Adhesion; Cholesterol; Clathrin; Complement; Complex; Cytoplasmic Tail; Early Endosome; Endocytosis; Fractionation; Funding; GPI Membrane Anchors; Glycosylphosphatidylinositols; Grant; Ligand Binding; Link; Membrane; National Center for Research Resources; Nebraska; Nutrient; Parasites; Play; Post-Translational Protein Processing; Principal Investigator; Process; Protein Family; Proteins; Reaction; Receptor Signaling; Recycling; Regulation; Reporting; Research; Research Infrastructure; Resources; Role; Signal Transduction; Source; Sphingolipids; TFAP2A gene; Tertiary Protein Structure; United States National Institutes of Health; cell motility; cost; 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. 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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 内吞运输是多个细胞功能的关键。配体结合后，细胞表面受体的内在化和细胞内行线对于它们调节各种关键过程的能力至关重要，包括营养摄取，细胞粘附，细胞迁移和受体信号传导。内部化主要以依赖于网格蛋白和AP-2适配器复合物的方式发生。然而，据报道，越来越多的受体以非甲基蛋白独立的方式内化。这些受体的一个子集被称为糖基磷脂酰肌醇（GPI）锚定的蛋白质（GPI-APS），这是一种多样的蛋白质家族，经过翻译后修饰，将它们共价链接到GPI。缺乏细胞质尾巴的GPIAP是在富含胆固醇和鞘脂的膜中组织的，这些区域被称为“筏”，因为它们的生物化学梯度分离中的浮力。在这里，我们假设新确定的C端EPS15同源域（EHD）蛋白在GPI-AP贩运中起关键作用。我们为EHD1的新功能提供了令人信服的初步证据，该功能在GPIAPS从早期内体转移到内吞回收室的运输，并解决了GPI-AP内吞作用调节的机制。由于GPIAP对于补体反应，寄生虫进入和细胞迁移等多种细胞过程至关重要，因此对GPI-AP运输的了解增强至关重要。