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.
