Poulter, Natalie S.Pollitt, Alice Y.Davies, AmyMalinova, DessislavaNash, Gerard B.Hannon, Mike J.Pikramenou, ZoeRappoport, Joshua Z.Hartwig, JohnOwen, Dylan M.Thrasher, Adrian J.Watson, Stephen P.Thomas, Steven G.2015-07-132015Poulter, N. S., A. Y. Pollitt, A. Davies, D. Malinova, G. B. Nash, M. J. Hannon, Z. Pikramenou, et al. 2015. “Platelet actin nodules are podosome-like structures dependent on Wiskott–Aldrich syndrome protein and ARP2/3 complex.” Nature Communications 6 (1): 7254. doi:10.1038/ncomms8254. http://dx.doi.org/10.1038/ncomms8254.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:17295613The 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.en-USJournal Article2015-07-1310.1038/ncomms8254