Transport of Proteins and RNAs in and out of the Nucleus

tors by the specific names used in their original descriptions. These receptors are generally large (90–130 kDa) Philadelphia, Pennsylvania 19104-6148 acidic proteins sharing 15%–25% sequence identity within a given organism. They all have an N-terminal RanGTP-binding domain, a C-terminal cargo-binding Eukaryotic cells are equipped with a machinery charged domain, and the capacity to bind components of the with the responsibility of transporting a vast number of NPC (Figure 1A). molecules in and out of the nucleus in a rapid, accurate, Many classes of cargo contain signals that bind di-and often regulated manner. The cargos for this machin-rectly to a cognate receptor, but three types have signals ery are diverse, comprising proteins and more elaborate that bind to the importin ␤ receptor indirectly, via adap-RNA–protein complexes (RNPs). Although the extent tor proteins. These are proteins with classical basic and complexity of trafficking between the nucleus and NLSs (either simple or bipartite) that bind the importin the cytoplasm have long been appreciated, it is only Proteins and some RNPs that need to move between replication protein A that binds the RIP␣ adaptor (Jullien the nucleus and cytoplasm in order to perform their et al., 1999). As all adaptor-utilizing cargos identified so normal cell functions are most often recognized by solu-far are imported by the importin ␤ receptor, they share an ble proteins, the nuclear transport receptors. These re-N-terminal importin ␤–binding (IBB) domain (Figure 1B). ceptors mediate translocation of cargos through the A variation of the simple receptor–import cargo mech-nuclear pore complex (NPC), the route for all macromo-anism is illustrated by the import of histone H1. This is lecular traffic across the nuclear membrane. After de-mediated by a dimeric complex of two receptors, im-positing their cargos in the appropriate compartment, portin ␤ and importin 7, in which importin 7 behaves like the unloaded receptors shuttle back through the NPC an adaptor or coreceptor (Jakel et al., 1999). Importin 7 to pick up more cargo. Like many vectorial cellular pro-can exist in either coreceptor or receptor mode, and as cesses, directionality is imposed on nucleocytoplasmic a receptor it functions in ribosomal protein import (Jakel traffic (at least in part) by a nucleotidase, the small and Gorlich, 1998). This phenomenon of receptors func-GTPase Ran. tioning in pairs might not be a quirk of importin 7: another Several experimental approaches, including in vitro receptor family member, importin 8, heterodimerizes import and export assays in higher eukaryotic …