Cse1p is required for export of Srp1p/importin-alpha from the nucleus in Saccharomyces cerevisiae

In metazoan cells, the CAS protein has been shown to function as a recyclin g factor for the importin-alpha subunit of the classical nuclear localizati on signal receptor, exporting importin-alpha from the nucleus to allow its participation in multiple rounds of nuclear import. CAS is a member of a fa mily of proteins that bear homology to the larger subunit of the nuclear lo calization signal receptor, importin-beta, and that are found in all eukary otes from yeast to humans. Sequence similarity identifies the product of th e Saccharomyces cerevisiae CSE1 gene as a potential CAS homologue. Here we present evidence that Cse1p is the functional homologue of GAS: Cse1p is re quired to prevent accumulation of Srplp/importin-a: in the nucleus, it loca lizes to the nuclear envelope in a pattern typical of nuclear transport rec eptors, and it associates in vivo with Srp1p in a nucleotide-specific manne r. We show further that mutations in CSE1 and SRP1 have specific effects on their association and on the intracellular localization of Cse1p.