Abstract
beta-Catenin is an example of a typical molecule that can be translocated bidirectionally through nuclear pore complexes (NPCs) on its own in a facilitated manner. In this work the nuclear import and export of beta-catenin were examined to compare the sequence requirement of this molecule and to determine whether molecular interactions required for its bidirectional NPC passage are distinct or not. Deletion analysis of beta-catenin revealed that armadillo repeats 10-12 and the C terminus comprise the minimum region necessary for nuclear migration activity. Further dissection of this fragment showed that the C terminus tail plays an essential role in nuclear migration. The region of beta-catenin required for export substantially overlapped the region required for import. Therefore, the NPC translocation of beta-catenin is apparently reversible, which is consistent with findings reported previously. However, different translocating molecules blocked nuclear import and export of beta-catenin differentially. The data herein indicate that beta-catenin shows an overlapping sequence requirement for its import and export but that bidirectional movement through the NPC proceeds through distinct molecular interactions.
Highlights
The bidirectional exchange of macromolecules is mediated by the nuclear pore complex (NPC)1 embedded in lipid bilayers of the nuclear envelope
Importin  strongly inhibited both the import and export of -catenin in the absence of Ran and ATP, importin  inhibited only the export of -catenin in the presence of Ran and ATP (Fig. 7). These results provide additional evidence that the molecular interactions required for -catenin import and export through the NPC are not identical, as discussed below. We and another group reported previously that -catenin is able to shuttle between the cytoplasm and the nucleus without the need for soluble factors or energy sources [18, 30]. -Catenin was shown to bind directly to the phenylalanine-glycine (FG) repeat-containing NPC components (FG-nucleoporins) [38]
The sequence requirement for import and export of -catenin was analyzed, and the findings indicate that ARM repeats 10 –12 and the C terminus tail of -catenin comprise a minimum region necessary for both the import and export that occur in a receptor-free manner (Figs. 2 and 4)
Summary
The bidirectional exchange of macromolecules is mediated by the nuclear pore complex (NPC) embedded in lipid bilayers of the nuclear envelope. The GTPase cycle of Ran, which generates RanGTP in the nucleus by the Ran guanine nucleotide exchange factor RCC1 (RanGEF) [10], and RanGDP in the cytoplasm by the Ran GTPase-activating protein (RanGAP) [11], creates a steep RanGTP gradient across the nuclear envelope [12] and assures the directional transport of importin/ exportin cargoes [13]. In addition to these receptors, the NXF family functions as a nuclear export receptor of mRNA (14 –16), and p10/NTF2 mediates the nuclear import of RanGDP to replenish nuclear Ran [17]. Because -catenin binds to many different proteins in both the cytoplasm and the nucleus, and its binding partners differ in different cells or
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