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

Natalie Poulter, Alice Pollitt, Amy Davies, Dessislava Malinova, Joshua Rappoport, Gerard Nash, Michael Hannon, Zoe Pikramenou, John H Hartwig, Adrian J Thrasher, Steve Watson, Steven Thomas, Dylan Owen

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)
193 Downloads (Pure)

Abstract

The actin nodule is a novel F-actin structure present in platelets during early spreading. However, only limited detail is known regarding nodule organisation and function. Here we use electron-microscopy, SIM and dSTORM super-resolution, and live-cell TIRF microscopy to characterise the structural organisation and signalling pathways associated with nodule formation. Nodules are composed of up to 4 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.
Original languageEnglish
Article number7254
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 1 Jun 2015

Keywords

  • Biological sciences
  • Cell biology

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