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

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, Stephen P. Watson*, Steven G. Thomas

*Corresponding author for this work

Research output: Contribution to journalArticle

49 Citations (Scopus)
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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.

Original languageEnglish
Article number7254
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 01 Jun 2015
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Poulter, N. S., Pollitt, A. Y., Davies, A., Malinova, D., Nash, G. B., Hannon, M. J., Pikramenou, Z., Rappoport, J. Z., Hartwig, J. H., Owen, D. M., Thrasher, A. J., Watson, S. P., & Thomas, S. G. (2015). Platelet actin nodules are podosome-like structures dependent on Wiskott-Aldrich syndrome protein and ARP2/3 complex. Nature Communications, 6, [7254]. https://doi.org/10.1038/ncomms8254