The active transport of proteins into and out of the nucleus is mediated by specific signals, the nuclear localzation signal (NLS) and nuclear export signal (NES), respectively. The best characterized NLS is that of the SV40 large T antigen, which contains a cluster of basic amino acids. The NESs were first identified in the protein kinase inhibitor (PKI) and HIV Rev protein, which are rich in leucine residues. The SV40 T-NLS containing transport substrates are carried into the nucleus by an importin α/β heterodimer. Importin α recognizes the NLS and acts as an adapter between the NLS and importin β, whereas importin β interacts with importin α bound to the NLS, and acts as a carrier of the NLS/importin α/β trimer. It is generally thought that importin α and β are part of a large protein family. The leucine rich NES-containing proteins are exported from the nucleus by one of the importin β family molecules, CRM1/exportin 1. A Ras-like small GTPase Ran plays a crucial role in both import/export pathways and determines the directionality of nuclear transport. It has recently been demonstrated in living cells that Ran actually shuttles between the nucleus and the cytoplasm and that the recycling of Ran is essential for the nuclear transport. Furthernore, it has been shown that nuclear transport factor 2 (NTF2) mediates the nuclear import of RanGDP. This review largely focuses on the issue concerning the functional divergence of importin α family molecules and the role of Ran in nucleocytoplasmic protein transport.
1999 by Japan Society for Cell Biology