F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets
Year: 2025
Type: article
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.
Source: Nature Communications
Authors: 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
Institutions: Inserm, Université Paris-Saclay, Centre National de la Recherche Scientifique, Institut Pasteur, Université Paris Cité, Biologie cellulaire physiologique et pathologique, Université de Tours, Centre Hospitalier Universitaire de Tours, Morphogénèse et antigénicité du VIH et des virus des hépatites et émergents, Analyse des Systèmes Biologiques, Optimisation Thérapeutique en Neuropsychopharmacologie, Lyon 1 Université, Hémostase & Thrombose, Centre Hospitalier Régional et Universitaire de Nancy, Biologie et pharmacologie des plaquettes sanguines : hémostase, thrombose, transfusion, Université de Strasbourg, Laboratoire de Recherche Vasculaire Translationnelle, Utrecht University, University Medical Center Utrecht, Institut Gustave Roussy, Cellules souches hématopoïétiques et développement des hémopathies myéloïdes, Innovations Thérapeutiques en Hémostase
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W4413094549