Several pathomechanisms are based on defects in the intracellular protein transport, which result from severe changes in the processing of membrane proteins and lipids in the highly polarized enterocytes. The current project will emphasize the role of lipid constituents of cellular membranes and carbohydrates compositions of several intestinal model proteins on the transport and sorting rates of these proteins in cell culture as well as in intestinal explants from healthy and diseased volunteers. The composition of the membranes will be modulated by fumonisin or ß-cyclodextrin which affects the biosynthesis of sphingolipids and cholesterol respectively. The posttranslational processing of carbohydrates will be influenced by inhibitors of ER- and Golgi-glucosidases, -mannosidases and -glycosyl-transferases. The data will be invaluable in characterization of the molecular basis of lipid microdomain formation in fully differentiated cells and along the proximal/distal axis in health and intestinal pathologies. The identification and characterisation of new genes that are implicated in protein-lipid interactions will further help unravel the complex mechanisms in intracellular transport.