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Borg proteins control septin organization and are negatively regulated by Cdc42

Nature Cell Biology volume 3, pages 861–866 (2001)Cite this article

Abstract

The Cdc42 GTPase binds to numerous effector proteins that control cell polarity, cytoskeletal remodelling and vesicle transport. In many cases the signalling pathways downstream of these effectors are not known. Here we show that the Cdc42 effectors Borg1 to Borg3 bind to septin GTPases. Endogenous septin Cdc10 and Borg3 proteins can be immunoprecipitated together by an anti-Borg3 antibody. The ectopic expression of Borgs disrupts normal septin organization. Cdc42 negatively regulates this effect and inhibits the binding of Borg3 to septins. Borgs are therefore the first known regulators of mammalian septin organization and provide an unexpected link between the septin and Cdc42 GTPases.

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Figure 1: Borgs interact directly with septins.
Figure 2: Borg3 binds septins via its BD3 domain.
Figure 3: Detection of Borg3–septin interaction in vivo by immunoblotting.
Figure 4: Localization of endogenous septins in MDCK epithelial cells by indirect immunofluorescence microscopy.
Figure 5: Borg3 controls the organization status of septins in MDCK cells.
Figure 6: Cdc42-GTP negatively regulates binding of Borg3 to septins.
Figure 7: Ectopic expression of activated Cdc42 causes a loss of septin filaments.

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Acknowledgements

We thank P. Silver for the gift of anti-GFP antibody. This work was supported by grants from the National Institutes of Health, DHHS, to I.G.M. and T.J.H.

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Author notes

  1. Gérard Joberty and Richard R. Perlungher: Both authors contributed equally to this work

Authors and Affiliations

  1. Markey Center for Cell Signaling and Department of Pharmacology, University of Virginia, Charlottesville, 22908, Virginia, USA

    Gérard Joberty, Richard R. Perlungher, Peter J. Sheffield & Ian G. Macara

  2. Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto, Japan

    Makoto Kinoshita & Makoto Noda

  3. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Timothy Haystead

  4. Department of Cell Biology, Harvard Medical School, 250 Longwood Avenue SGM529, Boston, 02115, Massachusetts, USA

    Makoto Kinoshita

Authors
  1. Gérard Joberty
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Corresponding authors

Correspondence to Gérard Joberty or Ian G. Macara.

Additional information

This PDF replaces the previous online version published on August 31 2001. Label on Figure 2c has changed from (1-150)GPS-AAA to (1-150)LVL-AAA.

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Joberty, G., Perlungher, R., Sheffield, P. et al. Borg proteins control septin organization and are negatively regulated by Cdc42. Nat Cell Biol 3, 861–866 (2001). https://doi.org/10.1038/ncb1001-861

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