Objective Megalin and cubilin mediated endocytosis at the apical pole of proximal tubule epithelial cells constitute a major route for renal retrieval of several essential glomerular filtrate solutes such as proteins vitamins and calcium. Pathophysiological signific ance of these receptors is supported by the finding of low-molecular weight proteinuria in megalin knockout mice and in dogs that bear inherited disorder of cubilin intracellular trafficking although the structure of cubilin is normal. Recently two protein s possibly responsible for cubilin trafficking has been identified: amnionless and cubilin-binding protein. The aim of the study is a closer characterization of those proteins and their role in megalin/cubilin mediated endocytosis as well as disclosure of possible target molecules/interactions for pharmacological intervention preventing reabsorption of toxic molecules in the proximal tubule. The studies include identification of the proteins involved, their purification and analysis, characterization of the ir interactions and subcellular distribution as well as functional studies by molecular biology approaches and pharmacological targeting. The intimate knowledge of the molecular interactions involved in the endocytic process that will be gained from the pr esent study are essential for the development of new therapeutic approaches in nephrology that involve modulation of cubilin and megalin expression/function in order to prevent or attenuate tubular uptake of deleterious substances. The project is the furth er initiative of the applicant in his scientific training, which started in Department of Biochemistry in Poland and was followed by stay in the Department of Cell Biology in Denmark. During the stay in INSERM U538 (Membrane Traffic in Epithelial Cells) th e applicant will be provided with thorough training in cell culture and molecular biology techniques. Fields of science medical and health sciencesclinical medicinenephrologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepathologymedical and health sciencesclinical medicinetransplantationnatural sciencesbiological sciencesmolecular biology Keywords cubilin endocytosis megalin nephrotoxicity Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Call for proposal FP6-2004-MOBILITY-5 See other projects for this call Funding Scheme EIF - Marie Curie actions-Intra-European Fellowships Coordinator INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Address 101, rue de tolbiac Paris France See on map Links Website Opens in new window EU contribution € 0,00
