ABSTRACT
The past decade has witnessed major advances in our understanding of the mechanism and regulation of nucleo-cytoplasmic transport in vertebrates and yeast (reviewed in Macara, 2001; Ossareh-Nazari et al., 2001; Weis, 2002). This transport occurs through nuclear pore complexes (NPC), large supramolecular structures that span the double membrane of the nuclear envelope (NE). Ions and small molecules less than ~40 kDa can passively diffuse through aqueous channels that cross the NPC, however larger macromolecules (most proteins and ribonucleoprotein complexes) are translocated through the central channel of the NPC in a saturable and sequence-mediated process that is rapid and highly selective (Kuersten et al., 2001; Macara, 2001; Mattaj and Englmeier, 1998). This nucleo-cytoplasmic traffic has evolved to be functionally and mechanistically diversified: beyond being needed for basal replication, transcription and RNA processing, it also serves to regulate the cell cycle, transcriptional activation and repression in response to a variety of physiological and environmental stimuli, circadian rhythms and a number of other processes (Macara, 2001; Ossareh-Nazari et al., 2001; Weis, 2002; Yamamoto and Deng, 1999). The small GTPase Ran, a member of the ras superfamily, is key in this process, both in establishing compartmental identity and in providing directionality to transport.
