Biologjia Online

We show that the specific subcellular distribution of H- and Nras GTPases is generated by a constitutive de/reacylation cycle that operates on palmitoylated proteins, driving their rapid exchange between the plasma membrane (PM) and the Golgi. Depalmitoylation redistributes farnesylated Ras in all membranes followed by repalmitoylation and trapping at the Golgi from where it is redirected to the PM via the secretory pathway. This continuous cycle prevents Ras from nonspecific residence on endomembranes, thereby maintaining the specific intracellular compartmentalisation. The de/reacylation cycle also initiates Ras activation at the Golgi by transport of PM-localized Ras-GTP. Different de/repalmitoylation kinetics account for isoform-specific activation responses in response to growth factors.