The adapter importin-α provides flexible control of nuclear import at the expense of efficiency

Although there exists a large family of nuclear transport receptors (Karyopherins), the majority of known import cargoes use an adapter protein, Importin-α (Impα), which links the cargo to a karyopherin, Importin-β (Impβ). The reason for the existence of transport adapters is unknown. One hypothesis is that, as Impα re-export is coupled to GTP hydrolysis, it can drive a higher concentration of nuclear cargo than could be achieved by direct cargo binding to Importin-β. However, computer simulations predicted the opposite outcome, and showed that direct transport is faster than adapter-mediated transport. These predictions were validated experimentally. The data, together with previous analyses of nuclear protein import, suggest that the use of adapters such as importin-α provides the cell with increased dynamic range for control of nuclear import rates, but at the expense of efficiency.