F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets

Jean Solarz, Christelle Soukaseum, Stéphane Frémont, Sébastien Eymieux, Camilia Nabli, Christelle Repérant, Elisa Rossi, Jean-Claude Bordet, Cécile V. Denis, Pierre Mangin, Yacine Boulaftali, R. Jeroen Pasterkamp, Hana Raslova, Dominique Baruch, Frédéric Adam, Arnaud Echard () and Alexandre Kauskot ()
Additional contact information
Jean Solarz: Université Paris-Saclay
Christelle Soukaseum: Université Paris-Saclay
Stéphane Frémont: CNRS UMR3691
Sébastien Eymieux: Inserm
Camilia Nabli: Inserm
Christelle Repérant: Université Paris-Saclay
Elisa Rossi: Optimisation thérapeutique en neuropharmacologie, OTEN U1144
Jean-Claude Bordet: Université Claude Bernard Lyon
Cécile V. Denis: Université Paris-Saclay
Pierre Mangin: Université de Strasbourg
Yacine Boulaftali: Université Paris Cité
R. Jeroen Pasterkamp: Utrecht University
Hana Raslova: Université Paris Saclay
Dominique Baruch: Université Paris Cité
Frédéric Adam: Université Paris-Saclay
Arnaud Echard: CNRS UMR3691
Alexandre Kauskot: Université Paris-Saclay

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Mechano-dependent interactions are key to thrombus formation and hemostasis, enabling stable platelet adhesion to injured vessels. The interaction between von Willebrand factor (VWF) and the platelet receptor GPIb-IX-V is central to this process. While GPIbα connects to the actin cytoskeleton, whether actin dynamics are important for GPIbα function under hemodynamic, high shear conditions remains largely unknown. Here, we show that actin disassembly is critical for proper VWF-GPIbα binding under shear. Mechanistically, we identify the oxidoreductase MICAL1 as a shear-activated regulator that promotes local F-actin disassembly around the GPIb-IX-V complex. This enables its translocation to lipid rafts and reinforces VWF binding. MICAL1-deficient platelets display impaired adhesion, increased deformability under shear, and defective thrombus formation in vivo. Thus, MICAL1 drives shear-dependent actin remodeling that supports GPIb-IX-V mechanotransduction and platelet function. These findings uncover a role for actin oxidation in platelet adhesion, providing a connection between cytoskeletal redox control and platelet function during thrombus formation.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62487-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62487-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62487-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().