BIN1 regulates actin-membrane interactions during IRSp53-dependent filopodia formation

• DOI: 10.1038/s42003-024-06168-8
• Publication Date: 2024-05-09T19:02:21Z
• Authors: Laura Picas; Charlotte André-A...; Franck Comunale; Hugo Bousquet; Feng-Ching Tsai; Félix Rico; Paolo Maiuri; Julien Pernier; Stéphane Bodin; Anne-Sophie Nicot; Jocelyn Laporte; Patricia Bassereau; Bruno Goud; Cécile Gauthier-R...; Stéphanie Miserey
• Keywords: 570; BIN1; QH301-705.5; [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics; Nerve Tissue Proteins; [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; Article; Mice; 03 medical and health sciences; 616; [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]; Actin Recruitment; Humans; Animals; Pseudopodia; Biology (General); IRSp53; Adaptor Proteins, Signal Transducing; Filopodia; 0303 health sciences; Tumor Suppressor Proteins; Cell Membrane; Nuclear Proteins; [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry; Actins; [PHYS.COND.CM-SCM] Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft]; [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics; Molecular Biology/Biophysics; [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft]

AbstractAmphiphysin 2 (BIN1) is a membrane and actin remodeling protein mutated in congenital and adult centronuclear myopathies. Here, we report an unexpected function of this N-BAR domain protein BIN1 in filopodia formation. We demonstrated that BIN1 expression is necessary and sufficient to induce filopodia formation. BIN1 is present at the base of forming filopodia and all along filopodia, where it colocalizes with F-actin. We identify that BIN1-mediated filopodia formation requires IRSp53, which allows its localization at negatively-curved membrane topologies. Our results show that BIN1 bundles actin in vitro. Finally, we identify that BIN1 regulates the membrane-to-cortex architecture and functions as a molecular platform to recruit actin-binding proteins, dynamin and ezrin, to promote filopodia formation.