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Platelet actin nodules are podosome-like structures dependent on Wiskott–Aldrich syndrome protein and ARP2/3 complex
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Platelet actin nodules are podosome-like structures dependent on Wiskott–Aldrich syndrome protein and ARP2/3 complex
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Journal Article
Platelet actin nodules are podosome-like structures dependent on Wiskott–Aldrich syndrome protein and ARP2/3 complex
2015
Overview
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.
During early platelet spreading a novel F-actin structure forms, called the actin nodule. Here Poulter
et al.
demonstrate that actin nodule formation depends on WASp and the Arp2/3 complex, and using super-resolution microscopy they show that nodules bear a structural resemblance to podosomes.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Pub. Group
Subject
/ 14/19
/ 14/34
/ 14/63
/ 64/60
/ Actin Cytoskeleton - metabolism
/ Actin Cytoskeleton - ultrastructure
/ Actin-Related Protein 2-3 Complex - metabolism
/ Animals
/ Blood Platelets - metabolism
/ Blood Platelets - ultrastructure
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Platelet Aggregation - genetics
/ Science
/ Wiskott-Aldrich Syndrome - blood
/ Wiskott-Aldrich Syndrome - genetics
