β-Subunit of nuclear pore-targeting complex (importin-β) can be exported from the nucleus in a Ran-independent manner

Abstract

The nuclear export of importin-α is mediated by CAS, which is related to importin-β, whereas the mechanism for the export of importin-β remains unclear. In this study, we demonstrate that the nuclear export of importin- β is mediated by the nuclear pore complex-binding domain of this molecule. Insensitivity to leptomycin B indicates that its export is not mediated by a leucine-rich nuclear export signal-specific receptor, CRM1. Furthermore, the nuclear export of importin-β was not inhibited by co-injection with a GTPase-deficient Ran mutant (G19V). The cell line tsBN2 contains a temperature-sensitive point mutation in the RCC1 gene, which encodes a guanine nucleotide exchange factor of Ran. At the nonpermissive temperature, importin-β was exported from the nucleus of these cells, even when RanGAP1, a GTPase-activating protein for Ran, was co-injected. These results not only provide support for the view that Ran-dependent GTP hydrolysis is not required for the nuclear export of importin-β but also indicate that nuclear RanGTP is not essential for its export. As a result, we propose that importin-β can be recycled from the nucleus alone in a Ran-independent manner.