Palmitoylation pilots Ras to recycling endosomes

We recently showed that palmitoylated Ras proteins (H-Ras and N-Ras) localize intracellularly at recycling endosomes (REs) and that REs act as a way-station for Ras proteins as they move along the post-Golgi exocytic pathway to the plasma membrane (PM). Palmitoylation is essential for H-Ras/N-Ras targeting to REs. H-Ras requires two palmitoyl groups for RE targeting. A lack of either or both palmitoyl groups causes H-Ras to be mislocalized to the endoplasmic reticulum (ER), the Golgi apparatus, or the PM. In this commentary, we summarize recent progress about the Ras trafficking cycle between the endomembranes (endosomes/ER/ Golgi) and the PM. We further discuss (1) the critical determinants of RE targeting of lipidated proteins and (2) possible Ras-mediated signaling pathways that originate from REs.