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Platelet actin nodules are podosome-like structures dependent on Wiskott–Aldrich syndrome protein and ARP2/3 complex

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  • Natalie S. Poulter

    (Centre for Cardiovascular Sciences, The Medical School, University of Birmingham)

  • Alice Y. Pollitt

    (Centre for Cardiovascular Sciences, The Medical School, University of Birmingham)

  • Amy Davies

    (PSIBS doctoral training centre, School of Chemistry, University of Birmingham)

  • Dessislava Malinova

    (Molecular Immunology Unit, UCL Institute of Child Health)

  • Gerard B. Nash

    (Centre for Cardiovascular Sciences, The Medical School, University of Birmingham)

  • Mike J. Hannon

    (PSIBS doctoral training centre, School of Chemistry, University of Birmingham)

  • Zoe Pikramenou

    (School of Chemistry, University of Birmingham)

  • Joshua Z. Rappoport

    (The Center for Advanced Microscopy and Nikon Imaging Center, Morton 2-681, Northwestern University Feinberg School of Medicine)

  • John H. Hartwig

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

  • Dylan M. Owen

    (New Hunt’s House, King’s College London)

  • Adrian J. Thrasher

    (Molecular Immunology Unit, UCL Institute of Child Health)

  • Stephen P. Watson

    (Centre for Cardiovascular Sciences, The Medical School, University of Birmingham)

  • Steven G. Thomas

    (Centre for Cardiovascular Sciences, The Medical School, University of Birmingham)

Abstract

The actin nodule is a novel F-actin structure present in platelets during early spreading. However, only limited detail is known regarding nodule organization and function. Here we use electron microscopy, SIM and dSTORM super-resolution, and live-cell TIRF microscopy to characterize the structural organization and signalling pathways associated with nodule formation. Nodules are composed of up to four actin-rich structures linked together by actin bundles. They are enriched in the adhesion-related proteins talin and vinculin, have a central core of tyrosine phosphorylated proteins and are depleted of integrins at the plasma membrane. Nodule formation is dependent on Wiskott–Aldrich syndrome protein (WASp) and the ARP2/3 complex. WASp−/− mouse blood displays impaired platelet aggregate formation at arteriolar shear rates. We propose actin nodules are platelet podosome-related structures required for platelet–platelet interaction and their absence contributes to the bleeding diathesis of Wiskott–Aldrich syndrome.

Suggested Citation

  • Natalie S. Poulter & Alice Y. Pollitt & Amy Davies & Dessislava Malinova & Gerard B. Nash & Mike J. Hannon & Zoe Pikramenou & Joshua Z. Rappoport & John H. Hartwig & Dylan M. Owen & Adrian J. Thrasher, 2015. "Platelet actin nodules are podosome-like structures dependent on Wiskott–Aldrich syndrome protein and ARP2/3 complex," Nature Communications, Nature, vol. 6(1), pages 1-15, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8254
    DOI: 10.1038/ncomms8254
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