IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-01690-2.html
   My bibliography  Save this article

Critical role of the HDAC6–cortactin axis in human megakaryocyte maturation leading to a proplatelet-formation defect

Author

Listed:
  • Kahia Messaoudi

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy
    Paris7 Diderot University)

  • Ashfaq Ali

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy
    Paris7 Diderot University)

  • Rameez Ishaq

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy
    Paris7 Diderot University)

  • Alberta Palazzo

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy
    Paris7 Diderot University)

  • Dominika Sliwa

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy)

  • Olivier Bluteau

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy)

  • Sylvie Souquère

    (Institut Gustave Roussy)

  • Delphine Muller

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy)

  • Khadija M. Diop

    (Institut Gustave Roussy)

  • Philippe Rameau

    (Integrated Biology Core Facility)

  • Valérie Lapierre

    (Cell Therapy Unit)

  • Jean-Pierre Marolleau

    (Amiens Hospital, UPJV University EA4666)

  • Patrick Matthias

    (Friedrich Miescher Institute for Biomedical Research)

  • Isabelle Godin

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy)

  • Gérard Pierron

    (Institut Gustave Roussy)

  • Steven G. Thomas

    (The Medical School, University of Birmingham, Edgbaston
    Universities of Birmingham and Nottingham)

  • Stephen P. Watson

    (The Medical School, University of Birmingham, Edgbaston
    Universities of Birmingham and Nottingham)

  • Nathalie Droin

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy
    Institut Gustave Roussy)

  • William Vainchenker

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy)

  • Isabelle Plo

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy)

  • Hana Raslova

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy)

  • Najet Debili

    (UMR 1170, Equipe labellisée par la Ligue Nationale contre le Cancer
    Paris-Saclay University
    Gustave Roussy)

Abstract

Thrombocytopenia is a major side effect of a new class of anticancer agents that target histone deacetylase (HDAC). Their mechanism is poorly understood. Here, we show that HDAC6 inhibition and genetic knockdown lead to a strong decrease in human proplatelet formation (PPF). Unexpectedly, HDAC6 inhibition-induced tubulin hyperacetylation has no effect on PPF. The PPF decrease induced by HDAC6 inhibition is related to cortactin (CTTN) hyperacetylation associated with actin disorganization inducing important changes in the distribution of megakaryocyte (MK) organelles. CTTN silencing in human MKs phenocopies HDAC6 inactivation and knockdown leads to a strong PPF defect. This is rescued by forced expression of a deacetylated CTTN mimetic. Unexpectedly, unlike human-derived MKs, HDAC6 and CTTN are shown to be dispensable for mouse PPF in vitro and platelet production in vivo. Our results highlight an unexpected function of HDAC6–CTTN axis as a positive regulator of human but not mouse MK maturation.

Suggested Citation

  • Kahia Messaoudi & Ashfaq Ali & Rameez Ishaq & Alberta Palazzo & Dominika Sliwa & Olivier Bluteau & Sylvie Souquère & Delphine Muller & Khadija M. Diop & Philippe Rameau & Valérie Lapierre & Jean-Pierr, 2017. "Critical role of the HDAC6–cortactin axis in human megakaryocyte maturation leading to a proplatelet-formation defect," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01690-2
    DOI: 10.1038/s41467-017-01690-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-01690-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-01690-2?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:8:y:2017:i:1:d:10.1038_s41467-017-01690-2. 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.