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

Poulter, N. S., Pollitt, A. Y. ORCID: https://orcid.org/0000-0001-8706-5154, 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. and 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. ISSN 2041-1723 doi: 10.1038/ncomms8254

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/44786
Identification Number/DOI	10.1038/ncomms8254
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	Nature Publishing Group
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