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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 functions as an adapter to access the importin beta -dependent import pathway. In contrast to what is found for importin beta , several isoforms of importin alpha , which can be grouped into three subfamilies, exist in higher eucaryotes. We describe here a novel member of the human family, importin alpha 7. To analyze specific functions of the distinct importin alpha  proteins, we recombinantly expressed and purified five human importin alpha 's along with importin alpha  from Xenopus and Saccharomyces cerevisiae. 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 various importin alpha  proteins. When the substrates were tested singly, only the import of RCC1 showed a strong preference for one family member, importin alpha 3, whereas most of the other substrates were imported by all importin alpha  proteins with similar efficiencies. However, strikingly different substrate preferences of the various importin alpha  proteins were revealed when two substrates were offered simultaneously.

* Corresponding author. Mailing address: Universität Göttingen, Zentrum Biochemie und Molekulare Zellbiologie, Abt. Biochemie II, 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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