To initiate nuclear import, most nuclear localization signals must be recognized by nuclear import receptors, sometimes called importins, most of which are encoded by a family of related genes. Each family member encodes a receptor protein that can bind and transport the subset of cargo proteins containing the appropriate nuclear localization signal (Figure 12–11A). Nuclear import receptors do not always bind to nuclear proteins directly. Additional adaptor proteins can form a bridge between the import receptors and the nuclear localization signals on the proteins to be transported (Figure 12–11B). Some adaptor proteins are structurally related to nuclear import receptors, suggesting a common evolutionary origin. By using a variety of import receptors and adaptors, cells are able to recognize the broad repertoire of nuclear localization signals that are displayed on nuclear proteins.
The import receptors are soluble cytosolic proteins that bind both to the nuclear localization signal on the cargo protein and to the phenylalanine-glycine (FG) repeats in the unstructured domains of the channel nucleoporins that line the central pore. FG-repeats are also found in the cytoplasmic and nuclear fibrils. FG-repeats in the unstructured tangle of the pore are thought to do double duty. They interact weakly, which gives the protein tangle gel-like properties that impose a permeability barrier to large macromolecules, and they serve as docking sites for nuclear import receptors. FG-repeats line the path through the NPCs taken by the import receptors and their bound cargo proteins. According to one model of nuclear transport, the receptor–cargo complexes move along the transport path by repeatedly binding, dissociating, and then re-binding to adjacent FG-repeat sequences. In this way, the complexes may hop from one nucleoporin to another to traverse the tangled interior of the NPC in a random walk. As import receptors bind to FG-repeats during this journey, they would disrupt interaction between the repeats and locally dissolve the gel phase of the protein tangle that fills the pore, allowing the passage of the receptor–cargo complex. Once inside the nucleus, the import receptors dissociate from their cargo and return to the cytosol. As we will see, this dissociation only occurs on the nuclear side of the NPC and thereby confers directionality to the import process.
nuclear export Works like nuclear import, But in reverse
The nuclear export of large molecules, such as new ribosomal subunits and RNA molecules, occurs through NPCs and also depends on a selective transport
Figure 12–9 The function of a nuclear localization signal. immunofluorescence micrographs showing the cell location of sV40 virus T-antigen containing or lacking a short sequence that serves as a nuclear localization signal. (a) The normal T-antigen protein contains the lysine-rich sequence indicated and is imported to its site of action in the nucleus, as indicated by immunofluorescence staining with antibodies against the T-antigen.
T-antigen with an altered nuclear localization signal (a threonine replacing  a lysine) remains in the cytosol. (from
D.
Kalderon, B. roberts, W. richardson and a. smith, Cell 39:499–509, 1984. With permission from elsevier.)