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	Laura Picas, Julien Viaud, Kristine Schauer, Stefano Vanni, Karim Hnia, Vincent Fraisier, Aurélien Roux, Patricia Bassereau, Frédérique Gaits-Iacovoni, Bernard Payrastre, Jocelyn Laporte, Jean-Baptiste Manneville, Bruno Goud
Journal	Nature communications (Nat Commun) Vol. 5 Pg. 5647 (Dec 09 2014) ISSN: 2041-1723 [Electronic] England
PMID	25487648 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Adaptor Proteins, Signal Transducing BIN1 protein, human Fluorescent Dyes Lipid Bilayers Liposomes Nuclear Proteins Phosphatidylinositols Tumor Suppressor Proteins Green Fluorescent Proteins Dynamins
Topics	Adaptor Proteins, Signal Transducing (chemistry) Amino Acid Motifs Cell Membrane (chemistry) Dynamins (chemistry) Endocytosis Fluorescent Dyes (chemistry) Green Fluorescent Proteins (chemistry) HeLa Cells Humans Lipid Bilayers (chemistry) Liposomes (chemistry) Molecular Dynamics Simulation Muscles (metabolism) Nuclear Proteins (chemistry) Phosphatidylinositols (chemistry) Protein Binding Protein Structure, Tertiary Tumor Suppressor Proteins (chemistry)

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