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

Natalie S. Poulter; Alice Y. Pollitt; Amy Davies; Dessislava Malinova; Gerard B. Nash; Mike J. Hannon; Zoe Pikramenou; Joshua Z. Rappoport; John H. Hartwig; Dylan M. Owen; Adrian J. Thrasher; Stephen P. Watson; Steven G. Thomas

doi:10.1038/ncomms8254

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

Natalie S. Poulter, Alice Y. Pollitt, Amy Davies, Dessislava Malinova, Gerard B. Nash, Mike J. Hannon, Zoe Pikramenou, Joshua Z. Rappoport, John H. Hartwig, Dylan M. Owen, Adrian J. Thrasher, Stephen P. Watson^*, Steven G. Thomas

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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 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.

Original language	English
Article number	7254
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8254
Publication status	Published - 01 Jun 2015
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms8254Licence: CC BY

Platelet actin nodules are podosome-like structures dependent on Wiskott-Aldrich syndrome protein and ARP2/3 complex
Copyright 2020 the authors. This is an open access article published under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 3.26 MBLicence: CC BY

Dessi Malinova
- D.Malinovaqub.acuk
- School of Medicine, Dentistry and Biomedical Sciences - Senior Lecturer
- Wellcome Wolfson Institute for Experimental Medicine
Person: Academic

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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., & Thomas, S. G. (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 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.",

author = "Poulter, {Natalie S.} and Pollitt, {Alice Y.} and Amy Davies and Dessislava Malinova and Nash, {Gerard B.} and Hannon, {Mike J.} and Zoe Pikramenou and Rappoport, {Joshua Z.} and Hartwig, {John H.} and Owen, {Dylan M.} and Thrasher, {Adrian J.} and Watson, {Stephen P.} and Thomas, {Steven G.}",

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AU - Poulter, Natalie S.

AU - Pollitt, Alice Y.

AU - Davies, Amy

AU - Malinova, Dessislava

AU - Nash, Gerard B.

AU - Hannon, Mike J.

AU - Pikramenou, Zoe

AU - Rappoport, Joshua Z.

AU - Hartwig, John H.

AU - Owen, Dylan M.

AU - Thrasher, Adrian J.

AU - Watson, Stephen P.

AU - Thomas, Steven G.

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AB - 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.

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JF - Nature Communications

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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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