IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms5839.html
   My bibliography  Save this article

Spatial control of Cdc42 signalling by a GM130–RasGRF complex regulates polarity and tumorigenesis

Author

Listed:
  • Francesco Baschieri

    (University of Konstanz
    Biotechnology Institute Thurgau, University of Konstanz)

  • Stefano Confalonieri

    (Molecular Medicine for Care Program, European Institute of Oncology
    IFOM, Fondazione Istituto FIRC di Oncologia Molecolare)

  • Giovanni Bertalot

    (Molecular Medicine for Care Program, European Institute of Oncology)

  • Pier Paolo Di Fiore

    (Molecular Medicine for Care Program, European Institute of Oncology
    IFOM, Fondazione Istituto FIRC di Oncologia Molecolare
    Università degli Studi di Milano)

  • Wolfgang Dietmaier

    (University of Regensburg, Institute of Pathology and molecular diagnostics)

  • Marcel Leist

    (University of Konstanz)

  • Piero Crespo

    (Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas (CSIC)—Universidad de Cantabria—SODERCAN)

  • Ian G. Macara

    (Vanderbilt University)

  • Hesso Farhan

    (University of Konstanz
    Biotechnology Institute Thurgau, University of Konstanz)

Abstract

The small GTPase Cdc42 is a key regulator of polarity, but little is known in mammals about its spatial regulation and the relevance of spatial Cdc42 pools for polarity. Here we report the identification of a GM130–RasGRF complex as a regulator of Cdc42 at the Golgi. Silencing GM130 results in RasGRF-dependent inhibition of the Golgi pool of Cdc42, but does not affect Cdc42 at the cell surface. Furthermore, active Cdc42 at the Golgi is important to sustain asymmetric front–rear Cdc42-GTP distribution in directionally migrating cells. Concurrent to Cdc42 inhibition, silencing GM130 also results in RasGRF-dependent Ras-ERK pathway activation. Moreover, depletion of GM130 is sufficient to induce E-cadherin downregulation, indicative of a loss in cell polarity and epithelial identity. Accordingly, GM130 expression is frequently lost in colorectal and breast cancer patients. These findings establish a previously unrecognized role for a GM130–RasGRF–Cdc42 connection in regulating polarity and tumorigenesis.

Suggested Citation

  • Francesco Baschieri & Stefano Confalonieri & Giovanni Bertalot & Pier Paolo Di Fiore & Wolfgang Dietmaier & Marcel Leist & Piero Crespo & Ian G. Macara & Hesso Farhan, 2014. "Spatial control of Cdc42 signalling by a GM130–RasGRF complex regulates polarity and tumorigenesis," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5839
    DOI: 10.1038/ncomms5839
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms5839
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms5839?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5839. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.