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

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52 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
Pages (from-to)7254
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 1 Jun 2015

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