Big proteins Ran into import difficulties

The need for Ran and GTP in nuclear import reactions depends on the size of the imported cargo, according to new results by Lyman et al. (page 55), who show that large proteins in particular are susceptible to stalling mid-import when the small GTPase Ran is missing.

Imported proteins, in association with cargo receptors such as importin β or transportin, pass from one nucleoporin protein to another within the nuclear pore complex (NPC) on their way to the nucleoplasm. Ran was already known to help cargo detach from its receptor in the nucleus. The new results give Ran a second unexpected function within the center of the channel.

This function stems from the ability of RanGTP to bind to cargo receptors. When Ran or GTP was absent from importin α/β and transportin...