Evidence for Distinct Substrate Specificities of Importin alpha  Family Members in Nuclear Protein Import

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Molecular and Cellular Biology, November 1999, p. 7782-7791, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Evidence for Distinct Substrate Specificities of Importin $alpha$ Family Members in Nuclear Protein Import

Matthias Köhler,¹^,² Christian Speck,³ Marret Christiansen,⁴ F. Ralf Bischoff,⁵ Siegfried Prehn,⁴ Hermann Haller,¹ Dirk Görlich,⁶ and Enno Hartmann²^,⁷^,^*

Charité, Franz-Volhard-Klinik,¹ and Max-Delbrück-Centrum,² Berlin-Buch, Institut für Biochemie der Charité⁴ and MPI Molekulare Genetik,³ Berlin, Zentrum für Molekulare Biologie⁶ and Abteilung Molekulare Biologie der Mitose, Deutsches Krebsforschungszentrum,⁵ Heidelberg, and Abteilung Biochemie II, Zentrum Biochemie und Molekulare Zellbiologie, Georg August University Göttingen, Göttingen,⁷ Germany

Received 3 March 1999/Returned for modification 15 April 1999/Accepted 3 August 1999

Importin $alpha$ plays a pivotal role in the classical nuclear protein import pathway. Importin $alpha$ shuttles between nucleus and cytoplasm,binds nuclear localization signal-bearing proteins, and functionsas an adapter to access the importin $beta$ -dependent import pathway.In contrast to what is found for importin $beta$ , several isoformsof importin $alpha$ , which can be grouped into three subfamilies, existin higher eucaryotes. We describe here a novel member of the humanfamily, importin $alpha$ 7. To analyze specific functions of the distinctimportin $alpha$ proteins, we recombinantly expressed and purified fivehuman importin $alpha$ 's along with importin $alpha$ from Xenopus and Saccharomycescerevisiae. Binding affinity studies showed that all importin $alpha$ proteins from humans or Xenopus bind their import receptor (importin $beta$ ) and their export receptor (CAS) with only marginal differences.Using an in vitro import assay based on permeabilized HeLa cells,we compared the import substrate specificities of the variousimportin $alpha$ proteins. When the substrates were tested singly, onlythe import of RCC1 showed a strong preference for one family member,importin $alpha$ 3, whereas most of the other substrates were importedby all importin $alpha$ proteins with similar efficiencies. However,strikingly different substrate preferences of the various importin $alpha$ proteins were revealed when two substrates were offeredsimultaneously.

^* Corresponding author. Mailing address: Universität Göttingen, Zentrum Biochemie und Molekulare Zellbiologie, Abt. BiochemieII, Goßlerstr. 12d, 37073 Göttingen, Germany. Phone: 49 551 395989.Fax: 49 551 395958. E-mail: ennohart{at}mdc.berlin.de.

Molecular and Cellular Biology, November 1999, p. 7782-7791, Vol. 19, No. 11
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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Evidence for Distinct Substrate Specificities of Importin Family Members in Nuclear Protein Import

Evidence for Distinct Substrate Specificities of Importin $alpha$ Family Members in Nuclear Protein Import