A wide variety of proteins are modified by covalently linked fatty acids and/or prenyl groups which confer reversible association of the lipid-modified protein with membranes. Moreover, each distinct fatty acid or prenyl moiety provides particular information to assist proteins in finding their correct subcellular destination and biological function. The work in our laboratory is focused to gain new insights into the consequences of lipidation of proteins on their intracellular trafficking and subcellular distribution using as model proteins H-Ras (dually palmitoylated + farnesylated), K-Ras (farnesylated + ?basic motif?) and GAP-43 (dually palmitoylated). It will be described our recent results obtained by using biochemical assays and a combination of selective photobleaching techniques and time-lapse fluorescence microscopy in living epithelial cells. Our finding support and illustrate how lipid modification of proteins plays an important role in dictating precise intracellular movements within the cells going beyond that of a simple hydrophobic modification.
