What role does NTF2 play in nuclear transport?
Maintenance of steep Ran gradient requires continuous recycling of Ran between compartments after hydrolysis. Ran-GDP formed in cytoplasm diffuses poorly across pore and requires facilitated import. Nuclear transport factor 2, small 14 kilodalton homodimer forming beta-sandwich barrel with hydrophobic cavity, specifically binds Ran-GDP conformation with high affinity but excludes Ran-GTP because switch I and switch II regions adopt different positions blocking NTF2 interaction. NTF2-Ran-GDP complex interacts transiently with FG repeats of central nucleoporins Nup62, Nup58 and Nup54 via surface-exposed residues, translocating rapidly without karyopherin assistance. Inside nucleus, RCC1 catalyzes exchange of GDP for GTP, conformational change reduces NTF2 affinity, releasing Ran-GTP and freeing NTF2 to return alone to cytosol for another cycle. Deletion or temperature sensitive alleles of NTF2 cause cytoplasmic accumulation of Ran and collapse of both import and export, indicating essential housekeeping function. Unlike NXF1 exporting mRNA, peroxisomal Pex5 recognizing SKL or COPI mediating Golgi-ER retrieval, NTF2 exclusively recycles Ran-GDP ensuring availability of nuclear Ran-GTP for subsequent rounds of transport and mitotic functions like spindle assembly.
Ref: Stewart M et al., J Cell Biol 147: 1999, NTF2 Imports Ran-GDP into Nucleus.