Importin a can migrate into the nucleus in an importin ß- and Ran-independent manner.

A classical nuclear localization signal (NLS)-containing protein is transported into the nucleus via the formation of a NLS-substrate/importin α/β complex. In this study, we found that importin a migrated into the nucleus without the addition of importin α, Ran or any other soluble factors in an in vitro transport assay. A mutant importin a tacking the importin β-binding domain efficiently entered the nucleus. Competition experiments showed that this import pathway for importin a is distinct from that of importin β. These results indicate that importin a atone can enter the nucleus via a novel pathway in an importin β- and Ran-independent manner. Furthermore, this process is evolutionarily conserved as similar results were obtained in Saccharomyces cerevisiae. Moreover, the import rate of importin a differed among individual nuclei of permeabilized cells, as demonstrated by time-lapse experiments. This heterogeneous nuclear accumulation of importin a was affected by the addition of ATP, but not ATPγS. These results suggest that the nuclear import machinery for importin a at individual nuclear pore complexes may be regulated by reaction(s) that require ATP hydrolysis. [ABSTRACT FROM AUTHOR]