Abstract

The actin cytoskeleton powers membrane deformation during many cellular processes, such as migration, morphogenesis, and endocytosis [1, 2]. Phosphoinositides regulate the activities of many actin-binding proteins  (ABPs), including profilin, cofilin, Dia2, N-WASP, ezrin, and moesin [3]; however, underlying molecular mechanisms have remained elusive. Here, we applied a combination of biophysical assays [4,5] and atomistic molecular dynamics simulations to uncover the molecular principles by which ABPs interact with phosphoinositide-containing membranes. Our results reveal that ABPs show large differences in the affinities and dynamics of membrane interactions and in the ranges of phosphoinositide densities that they sense [6].In the second half of my talk, I will briefly provide evidence that adherens junctions of epithelial cells harbor lamellipodia-like, dynamic actin-based membrane protrusions. A membrane-remodeling BAR domain protein [7] together with ABP promotes the formation of these membrane protrusions that contribute to the integrity of cell–cell junctions in epithelial monolayers [Senju et al., submitted]. These results elucidate the physiological relevancies of the membrane-ABP interactions, and membrane-interaction mechanisms of ABPs evolved to precisely fulfill their specific cellular functions in cytoskeletal dynamics.