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

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. 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

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To link to this item 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
Refereed:Yes
Divisions:Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:44786
Publisher:Nature Publishing Group

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