BIN1/M-Amphiphysin2 induces clustering of phosphoinositides to recruit its downstream partner dynamin

• DOI: 10.1038/ncomms6647
• Publication Date: 2014-12-09T09:59:46Z
• Authors: Laura Picas; Julien Viaud; Kristine Schauer; Stefano Vanni; Karim Hnia; Vincent Fraisier; Aurélien Roux; Patricia Bassereau; Frédérique Gaits-...; Bernard Payrastre; Jocelyn Laporte; Jean-Baptiste Man...; Bruno Goud
• Keywords: Dynamins; 0301 basic medicine; info:eu-repo/classification/ddc/540; Muscles; Tumor Suppressor Proteins; Amino Acid Motifs; Cell Membrane; Green Fluorescent Proteins; Lipid Bilayers; Nuclear Proteins; Molecular Dynamics Simulation; Phosphatidylinositols; Endocytosis; Protein Structure, Tertiary; [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics; 03 medical and health sciences; [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]; ddc:540; Liposomes; Humans; Adaptor Proteins, Signal Transducing; Fluorescent Dyes; HeLa Cells; Protein Binding

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.