Ras GTPases are key signalling molecules in regulation of cell proliferation, growth and differentiation. Active when GTP bound but inactive when GDP bound, they are anchored to cell membranes by lipid groups attached to their C-termini. How GTP loading affects the behaviour of Ras in the membrane in vivo has been unclear, but Thomas Schmidt and co-workers now reveal that it can cause Ras to become confined to small microdomains of the membrane (). The authors have used state-of-the art methods to monitor diffusion of single H-Ras molecules fused to yellow fluorescent protein (YFP) in living cells. They find that H-Ras exists in slow- and fast-diffusing populations. However, they also show that, in the slow population, activated H-Ras mutants are restricted to small, 200-nm membrane microdomains; by contrast, inactive H-Ras mutants appear to diffuse freely. The authors then demonstrate that adding insulin to cells expressing wild-type H-Ras likewise causes the slow-moving H-Ras population to become confined to 200-nm microdomains. Schmidt and co-workers suggest this is because the actin cytoskeleton `traps' H-Ras-containing signalling complexes, which could insulate Ras signalling and generate specificity.
