Importin-beta modulates the permeability of the nuclear pore complex in a Ran-dependent manner
Soluble karyopherins of the importin-beta (imp beta) family use RanGTP to transport cargos directionally through the nuclear pore complex (NPC). Whether imp beta or RanGTP regulate the permeability of the NPC itself has been unknown. In this study, we identify a stable pool of imp beta at the NPC. A subpopulation of this pool is rapidly turned-over by RanGTP, likely at Nup153. imp beta, but not transportin-1 (TRN1), alters the pore's permeability in a Ran-dependent manner, suggesting that imp beta is a functional component of the NPC. Upon reduction of Nup153 levels, inert cargos more readily equilibrate across the NPC yet active transport is impaired. When purified imp beta or TRN1 are mixed with Nup153 in vitro, higher-order, multivalent complexes form. RanGTP dissolves the imp beta eNup153 complexes but not those of TRN1.Nup153. We propose that imp beta and Nup153 interact at the NPC's nuclear face to form a Ran-regulated mesh that modulates NPC permeability.