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

Abstract

Amphiphysin 2 (BIN1) is a membrane and actin remodeling protein mutated both in congenital and adult centronuclear myopathies. The BIN1 muscle-specific isoform finely tunes muscle regeneration in adulthood and regulates myoblast fusion. However, the underlying molecular mechanisms are unknown. Here, we report that BIN1 is required for myoblast fusion and participates in the formation of filopodia-like structures at myoblasts intercellular junctions. BIN1 bundles actin in vitro and regulates the membrane-to-cortex attachment, two key processes required for myoblast fusion. We identified ezrin as a new BIN1 partner and showed that BIN1 promotes ezrin association to PI(4,5)P2 at the membrane cortex. Our results establish BIN1 and ezrin as key players at the early stages of myoblast fusion for the formation of long-lived filopodia-like structures.

Filopodia In Vitro and In Vivo

“…It is released from autoinhibition by phosphorylation and therefore is a candidate protein for transducing signals to changes in actin architecture (Gandy et al 2013, Tsai et al 2018). Depending on the binding partner, ezrin localizes to negatively curved membrane with IRSp53 (Tsai et al 2018) or positively curved membrane at the base of myoblast filopodia-like structures with N-BAR protein BIN1 (Picas et al 2022).…”