Like taxis waiting for a fare, importin-β molecules gather outside nuclear pores, ready to pick up cargoes and haul them into the nucleus. The protein RanBP2 helps corral these importin-β molecules, Hamada et al. reveal.
RanBP2 does double duty in the cell. During interphase, it forms the long filaments that protrude from the cytoplasmic side of a nuclear pore. During mitosis, it helps ensure that the chromosomes separate properly. Cells lacking the protein often show faulty spindles and misaligned chromosomes, whereas cells with abnormally low levels of RanBP2 are prone to aneuploidy.
To find out more about how RanBP2 performs its functions, Hamada et al. inactivated the gene in mouse embryonic fibroblasts. Cells lacking the protein died after 8–10 days, the researchers found. But they didn't die during or shortly after mitosis, suggesting that RanBP2’s mitotic role isn't essential. Instead, the researchers think that the cause of death is disrupted transport across the nuclear pores. Export of mRNA and other cargoes fell in the RanBP2-lacking cells, as did import of cargoes that use transportin 1 and importin-β as receptors.
Hamada et al. determined that the presence of one Ran-GTPase–binding domain in RanBP2 was crucial for cell survival and cargo transportation by importin-β, which carries a Ran-GTP complex. The researchers think that the Ran-binding domain on RanBP2 helps snare importin-β complexes as they return to the cytoplasm from a trip into the nucleus. This interaction detains importin-β molecules in a location where they can pick up another load.