TRANSPORTIN - NUCLEAR TRANSPORT RECEPTOR OF A NOVEL NUCLEAR-PROTEIN IMPORT PATHWAY

Many nuclear proteins are imported into the cell nucleus by the ''clas sical'' nuclear localization signal (NLS)-mediated import pathway. In this pathway, a sequence rich in basic residues in the protein interac ts with a heterodimeric complex termed importin and this, along with t he GTPase Ran, mediates nuclear import of the NLS-bearing protein. The heterogeneous nuclear ribonucleoprotein (hnRNP) Al protein contains a novel nuclear localization sequence, termed M9, that does not contain any clusters of basic residues. Very recently, we showed that M9 dire cts import into the nucleus by a novel protein import pathway distinct from the classical NLS pathway. A 90-kilodalton protein termed transp ortin was identified as a protein that specifically interacts with wil d-type M9 but not transport-defective MS mutants. Transportin and an A TP-regenerating system were found to be necessary and sufficient for i mport of MS-containing proteins in an in vitro import assay. In this r eport, we provide additional evidence that transportin can interact di rectly with MS-containing proteins and also show that it can mediate i mport of full-length hnRNP A1. In addition, Ran, or a Ran-binding prot ein, is identified as a second protein component of this novel nuclear import pathway. Transportin relatives from Saccharomyces cerevisiae w hich likely serve as additional nuclear transport receptors are descri bed. (C) 1996 Academic Press, Inc.