FG-centric versus Kap-centric NPC transport models. (Left) FG-centric models explain that an FG Nup barrier regulates selective transport through the NPC without invoking Kap occupancy. (Right) Kap-centric control argues that NPC barrier and transport function is regulated by Kaps in the pore. This is mediated by Kapα, which promotes NLS-cargo·Kapα·Kapβ1 import by switching the transport complex into a high-affinity FG Nup binding state. Upon reaching the nucleus, RanGTP switches Kapβ1 back to its lower affinity state while concomitantly releasing NLS-cargo and Kapα. At steady state, RanGTP·Kapβ1 export is sustained because it does not cross react with Kapα·Kapβ1 within the NPC. The model is constructed according to the equilibrium dissociation constants summarized in Table S4.