Several Phenylalanine-Glycine Motives in the Nucleoporin Nup214 Are Essential for Binding of the Nuclear Export Receptor CRM1

Nucleoporins containing phenylalanine glycine (FG) repeats play an important role in nucleocytoplasmic transport as they bind to transport receptors and mediate translocation of transport complexes across the nuclear pore complex (NPC). Nup214/CAN, a nucleoporin that is found at the cytoplasmic side of the NPC, interacts with both import and export receptors. In functional assays, dominant-negative fragments of Nup214 inhibited CRM1-dependent nuclear export, as the export receptor became rate-limiting. Several nuclear import pathways, by contrast, were not affected by the Nup214 fragments. We now characterize the CRM1-binding region of Nup214 in detail and identify several FG motives that are required for this interaction. Our results support a model where CRM1, like other transport receptors, contacts FG-Nups via multiple binding sites. Background: Nup214 interacts with the nuclear export receptor CRM1 and promotes export of certain cargos. Results: Several FG motives in the C-terminal region participate in CRM1 binding. Conclusion: CRM1, like other transport receptors, makes multiple contacts to nucleoporins. Significance: Elucidation of the details of nucleoporin-receptor interactions is essential for our understanding of the transition process of transport complexes through the nuclear pore.