IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v4y2013i1d10.1038_ncomms3863.html
   My bibliography  Save this article

Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics

Author

Listed:
  • Lisa Buvall

    (Harvard Medical School, Massachusetts General Hospital)

  • Priyanka Rashmi

    (Harvard Medical School, Massachusetts General Hospital
    Present address: Division of Nephrology, Department of Medicine, University of California, San Francisco, California 94143, USA)

  • Esther Lopez-Rivera

    (Mount Sinai School of Medicine)

  • Svetlana Andreeva

    (Harvard Medical School, Massachusetts General Hospital)

  • Astrid Weins

    (Harvard Medical School, Massachusetts General Hospital
    Harvard Medical School, Brigham and Women’s Hospital)

  • Hanna Wallentin

    (Harvard Medical School, Massachusetts General Hospital)

  • Anna Greka

    (Harvard Medical School, Massachusetts General Hospital)

  • Peter Mundel

    (Harvard Medical School, Massachusetts General Hospital)

Abstract

The ubiquitously expressed adapter proteins Nck1/2 interact with a multitude of effector molecules to regulate diverse cellular functions including cytoskeletal dynamics. Here we show that Nck1, but not Nck2, is a substrate of c-Cbl-mediated ubiquitination. We uncover lysine 178 in Nck1 as the evolutionarily conserved ubiquitin acceptor site. We previously reported that synaptopodin, a proline-rich actin-binding protein, induces stress fibres by blocking the Smurf1-mediated ubiquitination of RhoA. We now find that synaptopodin competes with c-Cbl for binding to Nck1, which prevents the ubiquitination of Nck1 by c-Cbl. Gene silencing of c-Cbl restores Nck1 protein abundance and stress fibres in synaptopodin knockdown cells. Similarly, expression of c-Cbl-resistant Nck1(K178R) or Nck2 containing the SH3 domain 2 of Nck1 restores stress fibres in synaptopodin-depleted podocytes through activation of RhoA signalling. These findings reveal proteasomal regulation as a key factor in the distinct and non-redundant effects of Nck on RhoA-mediated actin dynamics.

Suggested Citation

  • Lisa Buvall & Priyanka Rashmi & Esther Lopez-Rivera & Svetlana Andreeva & Astrid Weins & Hanna Wallentin & Anna Greka & Peter Mundel, 2013. "Proteasomal degradation of Nck1 but not Nck2 regulates RhoA activation and actin dynamics," Nature Communications, Nature, vol. 4(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3863
    DOI: 10.1038/ncomms3863
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms3863
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms3863?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Masahiro Takahashi & Shinya Yamamoto & Shigenori Yamamoto & Akihiro Okubo & Yasuaki Nakagawa & Koichiro Kuwahara & Taiji Matsusaka & Shingo Fukuma & Masamichi Yamamoto & Michiyuki Matsuda & Motoko Yan, 2024. "ATP dynamics as a predictor of future podocyte structure and function after acute ischemic kidney injury in female mice," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

    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:4:y:2013:i:1:d:10.1038_ncomms3863. 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.