U.S.-Netherlands Cooperative Research: Cell Biology of Receptor Mediated Endocytosis

这是密苏里州圣路易斯华盛顿大学医学院儿科学教授和药理学教授Alan L. Schwartz教授与荷兰乌得勒支大学电子显微镜中心H. J. Geuze和G. J. a . M. Strous教授在细胞生物学领域开展的一项为期三年的合作研究项目。合作的科学家和他们的研究小组成员将继续努力阐明受体介导的内吞作用（RME）的细胞生物学，并从生化和形态学的角度定义这一过程。研究人员将使用肝asialal糖蛋白受体作为RME研究的模型。受体介导的内吞作用是细胞外大分子和颗粒进入细胞内环境的过程。这一过程负责细胞摄取和输送多种物质，包括必需的细胞营养素（如铁、维生素B-12）、毒素（如白喉毒素）、细胞生长因子/激素（如胰岛素）、病毒（如流感）和从循环中清除的蛋白质（如asialal糖蛋白）。这项合作研究预计将导致对细胞间通讯的分子基础和细胞外向细胞内传递生化信息的理解的增加。这种对RME基本生物学的理解将直接适用于阐明正常细胞中的细胞过程，并且为定向药物治疗的新方法提供基础背景。这里的方法将结合生化和分子生物学方面（施瓦茨教授的专业知识）和超微结构免疫细胞化学（荷兰研究人员的专业知识）。Geuze教授在乌得勒支的实验室配备了几台最先进的电子显微镜和超低温切片机，这些仪器将在本研究中使用。该奖金将用于支持美国首席研究员及其研究小组成员的必要交通和生活费用。荷兰政府也通过乌得勒支大学为该项目提供支持。

This is a three-year cooperative research project in cellular biology between Professor Alan L. Schwartz, Professor of Pediatrics and Professor of Pharmacology, Washington University School of Medicine, St. Louis, MO, and Professors H. J. Geuze and G. J. A. M. Strous, Center for Electron Microscopy, University of Utrecht, The Netherlands. The cooperating scientists and members of their research groups will continue their efforts to elucidate the cell biology of receptor mediated endocytosis (RME) and to define this process in both biochemical and morphological terms. The investigators will use the hepatic asialoglycoprotein receptor as their model for the study of RME. Receptor mediated endocytosis is a process by which extracellular macromolecules and particles gain entry to the intracellular environment. The process is responsible for the cellular uptake and delivery of a broad class of substances which include essential cell nutrients (e.g. iron, Vitamin B-12), toxins (e.g. diphtheria toxin), cell growth factors/hormones (e.g. insulin), viruses (e.g. influenza), and proteins undergoing clearance from the circulation (e.g. asialoglycoprotein). This cooperative study is expected to lead to an increased understanding of the molecular basis of cell-cell communication and the transfer of biochemical information from outside of a cell to within it. Such an understanding of the basic biology of RME would have direct applicability to the elucidation of cellular processes in normal cells, and in addition provide a background on which to base new approaches to directed drug therapy. The approach here will combine a biochemical and molecular biological aspect (Professor Schwartz's expertise) with ultrastructural immunocytochemistry (the expertise of the Dutch investigators). Professor Geuze's laboratory in Utrecht is equipped with several state-of-the-art electron microscopes and ultra-cryo microtomes which will be utilized in this study. Funds from this award will support necessary transportation and subsistence expenses for the U.S. principal investigator and members of his research group. The government of The Netherlands, through the University of Utrecht, is also providing support for the project.