F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets
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 cytoskelet...
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62487-2 |
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| author | 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 Alexandre Kauskot |
| author_facet | 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 Alexandre Kauskot |
| author_sort | Jean Solarz |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d2b5252b38b5421fac2dadfb7ff2da6f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-d2b5252b38b5421fac2dadfb7ff2da6f2025-08-20T03:46:25ZengNature PortfolioNature Communications2041-17232025-08-0116111910.1038/s41467-025-62487-2F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in plateletsJean Solarz0Christelle Soukaseum1Stéphane Frémont2Sébastien Eymieux3Camilia Nabli4Christelle Repérant5Elisa Rossi6Jean-Claude Bordet7Cécile V. Denis8Pierre Mangin9Yacine Boulaftali10R. Jeroen Pasterkamp11Hana Raslova12Dominique Baruch13Frédéric Adam14Arnaud Echard15Alexandre Kauskot16HITh, UMR_S1176, INSERM, Université Paris-SaclayHITh, UMR_S1176, INSERM, Université Paris-SaclayInstitut Pasteur, Université Paris Cité, CNRS UMR3691Microscopy facility, US61 ASB, University of Tours, University Hospital Center of Tours, InsermMicroscopy facility, US61 ASB, University of Tours, University Hospital Center of Tours, InsermHITh, UMR_S1176, INSERM, Université Paris-SaclayUniversité Paris-Cité, INSERM, Optimisation thérapeutique en neuropharmacologie, OTEN U1144UR4609 Hémostase & Thrombose, Université Claude Bernard LyonHITh, UMR_S1176, INSERM, Université Paris-SaclayINSERM U1255, Université de StrasbourgINSERM U1148, Université Paris CitéDepartment of Translational Neuroscience, University Medical Center Utrecht, Brain Center, Utrecht UniversityINSERM U1287, Institut Gustave Roussy, Université Paris SaclayINSERM U1140, Université Paris CitéHITh, UMR_S1176, INSERM, Université Paris-SaclayInstitut Pasteur, Université Paris Cité, CNRS UMR3691HITh, UMR_S1176, INSERM, Université Paris-SaclayAbstract 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.https://doi.org/10.1038/s41467-025-62487-2 |
| spellingShingle | 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 Alexandre Kauskot F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets Nature Communications |
| title | F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets |
| title_full | F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets |
| title_fullStr | F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets |
| title_full_unstemmed | F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets |
| title_short | F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets |
| title_sort | f actin disassembly by the oxidoreductase mical1 promotes mechano dependent vwf gpibα interaction in platelets |
| url | https://doi.org/10.1038/s41467-025-62487-2 |
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