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

Natalie Poulter; Alice Pollitt; Amy Davies; Dessislava Malinova; Joshua Rappoport; Gerard Nash; Michael Hannon; Zoe Pikramenou; John H Hartwig; Adrian J Thrasher; Steve Watson; Steven Thomas; Dylan Owen

doi:10.1038/ncomms8254

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

Natalie Poulter, Alice Pollitt, Amy Davies, Dessislava Malinova, Joshua Rappoport, Gerard Nash, Michael Hannon, Zoe Pikramenou, John H Hartwig, Adrian J Thrasher, Steve Watson, Steven Thomas, Dylan Owen

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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 organisation and function. Here we use electron-microscopy, SIM and dSTORM super-resolution, and live-cell TIRF microscopy to characterise the structural organisation and signalling pathways associated with nodule formation. Nodules are composed of up to 4 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 language	English
Article number	7254
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8254
Publication status	Published - 1 Jun 2015

Keywords

Biological sciences
Cell biology

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10.1038/ncomms8254Licence: Creative Commons: Attribution (CC BY)

PoulterN2015Platelet
Poulter, N., Pollitt, A., Davies, A. et al. Platelet actin nodules are podosome-like structures dependent on Wiskott–Aldrich syndrome protein and ARP2/3 complex. Nat Commun 6, 7254 (2015). https://doi.org/10.1038/ncomms8254
Final published version, 4.26 MBLicence: Creative Commons: Attribution (CC BY)

Development and Application of Dynamic Imaging of Adhesion, Spreading and Migration in Megakaryocytes/Platelets and Neutrophils
Watson, S. (Principal Investigator), Hannon, M. (Co-Investigator), Nash, G. (Co-Investigator), Rappoport, J. (Co-Investigator) & Thomas, S. (Co-Investigator)
British Heart Foundation
12/04/12 → 11/04/15
Project: Research
The Early Events in Signalling by Platelet ITAM and ITAM-Like Receptors
Watson, S. (Principal Investigator)
Wellcome Trust
1/08/09 → 31/03/16
Project: Research

Cite this

Poulter, N., Pollitt, A., Davies, A., Malinova, D., Rappoport, J., Nash, G., Hannon, M., Pikramenou, Z., Hartwig, J. H., Thrasher, A. J., Watson, S., Thomas, S., & Owen, D. (2015). Platelet actin nodules are podosome-like structures dependent on Wiskott-Aldrich Syndrome protein and ARP2/3 complex. Nature Communications, 6, Article 7254. https://doi.org/10.1038/ncomms8254

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title = "Platelet actin nodules are podosome-like structures dependent on Wiskott-Aldrich Syndrome protein and ARP2/3 complex",

abstract = "The actin nodule is a novel F-actin structure present in platelets during early spreading. However, only limited detail is known regarding nodule organisation and function. Here we use electron-microscopy, SIM and dSTORM super-resolution, and live-cell TIRF microscopy to characterise the structural organisation and signalling pathways associated with nodule formation. Nodules are composed of up to 4 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. ",

keywords = "Biological sciences, Cell biology",

author = "Natalie Poulter and Alice Pollitt and Amy Davies and Dessislava Malinova and Joshua Rappoport and Gerard Nash and Michael Hannon and Zoe Pikramenou and Hartwig, {John H} and Thrasher, {Adrian J} and Steve Watson and Steven Thomas and Dylan Owen",

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AU - Poulter, Natalie

AU - Pollitt, Alice

AU - Davies, Amy

AU - Malinova, Dessislava

AU - Rappoport, Joshua

AU - Nash, Gerard

AU - Hannon, Michael

AU - Pikramenou, Zoe

AU - Hartwig, John H

AU - Thrasher, Adrian J

AU - Watson, Steve

AU - Thomas, Steven

AU - Owen, Dylan

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N2 - The actin nodule is a novel F-actin structure present in platelets during early spreading. However, only limited detail is known regarding nodule organisation and function. Here we use electron-microscopy, SIM and dSTORM super-resolution, and live-cell TIRF microscopy to characterise the structural organisation and signalling pathways associated with nodule formation. Nodules are composed of up to 4 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.

AB - The actin nodule is a novel F-actin structure present in platelets during early spreading. However, only limited detail is known regarding nodule organisation and function. Here we use electron-microscopy, SIM and dSTORM super-resolution, and live-cell TIRF microscopy to characterise the structural organisation and signalling pathways associated with nodule formation. Nodules are composed of up to 4 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.

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KW - Cell biology

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JO - Nature Communications

JF - Nature Communications

M1 - 7254

ER -

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

Abstract

Keywords

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Projects

Development and Application of Dynamic Imaging of Adhesion, Spreading and Migration in Megakaryocytes/Platelets and Neutrophils

The Early Events in Signalling by Platelet ITAM and ITAM-Like Receptors

Cite this