F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets
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.
Authors
- Hana Raslová (ORCID: https://orcid.org/0000-0001-8846-5299)
- Christelle Repérant
- Cécile V. Denis (ORCID: https://orcid.org/0000-0001-5152-9156)
- Pierre Mangin (ORCID: https://orcid.org/0000-0001-9522-6261)
- Dominique Baruch (ORCID: https://orcid.org/0000-0003-2835-5500)
- Jean‐Claude Bordet (ORCID: https://orcid.org/0000-0003-1498-703X)
- Stéphane Frémont (ORCID: https://orcid.org/0000-0002-5799-5630)
- R. Jeroen Pasterkamp (ORCID: https://orcid.org/0000-0003-1631-6440)
- Arnaud Échard (ORCID: https://orcid.org/0000-0001-7402-1398)
- Jean Solarz (ORCID: https://orcid.org/0000-0003-3282-2976)
- Alexandre Kauskot (ORCID: https://orcid.org/0000-0002-4064-8114)
- Elisa Rossi (ORCID: https://orcid.org/0000-0002-0570-6104)
- Sébastien Eymieux (ORCID: https://orcid.org/0000-0002-4738-510X)
- Christelle Soukaseum (ORCID: https://orcid.org/0000-0002-5976-1424)
- Yacine Boulaftali (ORCID: https://orcid.org/0000-0003-4870-2098)
- Frédéric Adam (ORCID: https://orcid.org/0000-0001-6603-2687)
- Camilia Nabli
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Université de Tours (FR)
- Délégation Paris 5 (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Utrecht University (NL)
- Université Paris Cité (FR)
- Université Paris-Saclay (FR)
- Institut Gustave Roussy (FR)
- University Medical Center Utrecht (NL)
- Sorbonne Paris Cité (FR)
- Université de Strasbourg (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-10
- DOI
- https://doi.org/10.1038/s41467-025-62487-2
- Primary Topic
- Platelet Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Centre National de la Recherche Scientifique