title: BIN1/M-Amphiphysin2 induces clustering of phosphoinositides to recruit its downstream partner dynamin.
abstract: Phosphoinositides play a central role in many physiological processes by assisting the recruitment of proteins to membranes through specific phosphoinositide-binding motifs. How this recruitment is coordinated in space and time is not well understood. Here we show that BIN1/M-Amphiphysin2, a protein involved in T-tubule biogenesis in muscle cells and frequently mutated in centronuclear myopathies, clusters PtdIns(4,5)P2 to recruit its downstream partner dynamin. By using several mutants associated with centronuclear myopathies, we find that the N-BAR and the SH3 domains of BIN1 control the kinetics and the accumulation of dynamin on membranes, respectively. We show that phosphoinositide clustering is a mechanism shared by other proteins that interact with PtdIns(4,5)P2, but do not contain a BAR domain. Our numerical simulations point out that clustering is a diffusion-driven process in which phosphoinositide molecules are not sequestered. We propose that this mechanism plays a key role in the recruitment of downstream phosphoinositide-binding proteins.
authors.affiliation: Institut Curie and CNRS UMR 144, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Laura
authors.initials: L
authors.lastname: Picas
authors.affiliation: INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 1 avenue Jean Poulhès, 31432 Toulouse, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Viaud
authors.affiliation: Institut Curie and CNRS UMR 144, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Kristine
authors.initials: K
authors.lastname: Schauer
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire, Université de Nice Sophia-Antipolis and Centre National de la Recherche Scientifique, UMR 7275, 06560 Valbonne, France.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vanni
authors.affiliation: Department of Translational Medicine, IGBMC, U964, UMR7104, Strasbourg University, Collège de France, 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Hnia
authors.affiliation: Institut Curie and CNRS UMR 144, Cell and Tissue Imaging Platform, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fraisier
authors.affiliation: Biochemistry Department, University of Geneva, 30 quai Ernest Ansermet, 1211 Geneva, Switzerland.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Roux
authors.affiliation: Institut Curie and CNRS UMR 168, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Bassereau
authors.affiliation: INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 1 avenue Jean Poulhès, 31432 Toulouse, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Gaits-Iacovoni
authors.affiliation: INSERM, UMR1048, Université Toulouse III, Institut des Maladies Métaboliques et Cardiovasculaires, 1 avenue Jean Poulhès, 31432 Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
authors.affiliation: Department of Translational Medicine, IGBMC, U964, UMR7104, Strasbourg University, Collège de France, 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Laporte
authors.affiliation: Institut Curie and CNRS UMR 144, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Manneville
authors.affiliation: Institut Curie and CNRS UMR 144, 26 rue d'Ulm, 75005 Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Goud
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry*; D020816:Amino Acid Motifs; D002462:Cell Membrane / Q000737:chemistry; D034281:Dynamins / Q000737:chemistry*; D004705:Endocytosis; D005456:Fluorescent Dyes / Q000737:chemistry; D049452:Green Fluorescent Proteins / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D009132:Muscles / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry*; D010716:Phosphatidylinositols / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D025521:Tumor Suppressor Proteins / Q000737:chemistry*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008081:Liposomes; D009687:Nuclear Proteins; D010716:Phosphatidylinositols; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins; D034281:Dynamins