Welf et al. discover the necessity of membrane-actin bond release for cell protrusion initiation

In a collaborative effort, Welf et al. discovered that separation of the cell membrane from an existing actin network is required to initiate the molecular events that lead to cell shape change. By studying the dynamic localization and function of a canonical actin-membrane linker protein, ezrin, they found that local ezrin concentration decreases before these shape change events. Likewise, biochemical perturbations that increase ezrin localization decrease shape change whereas perturbations that decrease ezrin localization increase them. Construction of a theoretical model for how such actin-membrane linkages interact with the classical Brownian Ratchet model for force generation by actin polymerization provided further insight into regulated shape change. They found that intrinsic fluctuations in actin-membrane links create “seed points” whereby local actin polymerization can occur faster than areas with tight actin-membrane links. Thus, actin-membrane linkage works in concert with actin polymerization to create a multivariate regulatory mechanism for cell shape change.