The yeast nucleoporin Nup2p is involved in nuclear export of importin alpha/Srp1p

The importin alpha.beta heterodimer mediates nuclear import of proteins con taining classical nuclear localization signals, After carrying its cargo in to the nucleus, the importin dimer dissociates, and Srp1p (the yeast import in cu subunit) is recycled to the cytoplasm in a complex with Cse1p and Ran GTP. Nup2p is a yeast FXFG nucleoporin that contains a Ran-binding domain. We find that export of Srp1p from the nucleus is impaired in Delta nup2 mut ants. Also, Srp1p fusion proteins accumulate at the nuclear rim in wild-typ e cells but accumulate in the nuclear interior in Delta nup2 cells. A delet ion of NUP2 shows genetic interactions with mutants in SRP1 and PRP20, whic h encodes the Ran nucleotide exchange factor. Srp1p binds directly to an N- terminal domain of Nup2p. This region of Nup2p is sufficient to allow accum ulation of an Srp1p fusion protein at the nuclear rim, but the C-terminal R an-binding domain of Nup2p is required for efficient Srp1p export. Formatio n of the Srp1p Cse1p RanGTP export complex releases Srp1p from its binding site in Nup2p. me propose that Nup2p may act as a scaffold that facilitates formation of the Srp1p export complex.