Ras proteins are restless, continually flitting from the cell membrane to the Golgi apparatus and back again. Misaki et al. reveal that the proteins enter recycling endosomes during the journey to the plasma membrane.
One mystery is why Ras proteins—which spur cell growth, differentiation, and survival—move so often. The cluttered cell interior has also made it difficult to discern how the proteins travel. Proteins heading for the Golgi might zip through the cytosol or hitchhike in endosomes. Some evidence suggests that they pass through recycling endosomes, whereas other studies indicate they shun the endocytic pathway altogether.
Misaki et al. used COS-1 cells in which recycling endosomes are easier to observe because they gather in the so-called Golgi ring near the organelle, separate from early and late endosomes. The researchers found that Ras proteins do spend time in recycling endosomes, but only on the outbound leg from the Golgi to the cell membrane. Addition of two palmitoyl groups directs Ras to recycling endosomes, the team discovered.
The researchers think that an unidentified vesicle ferries the proteins from the Golgi to the recycling endosomes. Whether recycling endosomes deliver Ras proteins to the cell membrane or hand off their cargo to other carriers is unclear. Receptors such as the epidermal growth factor receptor also slip into recycling endosomes and might activate Ras proteins there.