The mechanism of facilitated translocation through nuclear pore complexes (
NPCs) is only poorly understood. Here, we present a kinetic analysis of the
process using various model substrates. We find that the translocation cap
acity of NPCs is unexpectedly high, with a single NPC allowing a mass flow
of nearly 100 MDa/s and rates in the order of 10(3) translocation events pe
r second. Our data further indicate that high affinity interactions between
the translocation substrate and NPC components are dispensable for translo
cation, We propose a 'selective phase model' that could explain how NPCs fu
nction as a permeability barrier for inert molecules and yet become selecti
vely permeable for nuclear transport receptors and receptor-cargo complexes
.