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

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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
Pages (from-to)	7254
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8254
Publication status	Published - 1 Jun 2015

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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, 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.}",

note = "{"}We thank the British Heart Foundation (NH/11/6/29061 & CH/03/003SP1), Wellcome Trust (088410/Z/09/Z), EPSRC (EP/F50053X/1) and Great Ormond Street Hospital BRC for providing funding.{"}",

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doi = "10.1038/ncomms8254",

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T1 - Platelet actin nodules are podosome-like structures dependent on Wiskott-Aldrich syndrome protein and ARP2/3 complex

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.

N1 - "We thank the British Heart Foundation (NH/11/6/29061 & CH/03/003SP1), Wellcome Trust (088410/Z/09/Z), EPSRC (EP/F50053X/1) and Great Ormond Street Hospital BRC for providing funding."

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

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.

U2 - 10.1038/ncomms8254

DO - 10.1038/ncomms8254

M3 - Article

C2 - 26028144

SN - 2041-1723

VL - 6

SP - 7254

JO - Nature Communications

JF - Nature Communications

ER -

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

Abstract

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