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

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)P 2 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)P 2 , 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. BIN1/M-Amphiphysin2 is a membrane tubulating protein involved in muscle T-tubule biogenesis and whose loss-of-function is associated with centronuclear myopathies. Picas et al. show that BIN1 enhances the recruitment of its binding partner, dynamin, by clustering PtdIns(4,5)P2 in the plasma membrane.