A distinct nuclear import pathway used by ribosomal proteins.

Protein transport into the nucleus is governed by the interaction of soluble transport factors with their import substrates and nuclear pore complexes. Here, we identify a major distinct nuclear import pathway, mediated by a previously uncharacterized yeast beta karyopherin Kap123p. The predominant substrates for this pathway are ribosomal proteins, which must be imported into the nucleus prior to assembly into pre-ribosomes. Kap123p binds directly to its transport substrates, repeat motif-containing nucleoporins, and Ran-GTP. We show that the related protein Pse1p is also a karyopherin and can functionally substitute for Kap123p; both are capable of specifically directing a ribosomal nuclear localization signal reporter to the nucleus in vivo.