Actin-binding proteins take the reins in growth cones

Key Points To be effective in enabling growth-cone motility, actin filaments must be organized into higher-order assemblies with distinct architectures (actin superstructures). Actin superstructures are self-organizing. The cell-free Listeria monocytogenes comet-tail reconstitution assay demonstrated that a propulsive and dynamic actin superstructure can be self-organized by an ensemble of actin-binding proteins. Although they are classically defined only by their architectural appearance, actin superstructures can now be more subtly distinguished by their recruitment of specific ensembles of actin-binding proteins. Actin superstructure organization effectively occurs in a two-step process. As actin superstructures are self-organizing, the limiting step is actin-filament assembly itself. Not all of the proteins that are involved in generating or maintaining actin superstructures have been well characterized in growth cones. Leading-edge actin superstructures are organised into stratified layers. Because actin subunits incorporate into filaments at the leading-edge membrane, migrate away from the membrane at similar rates, and undergo ATP hydrolysis and P i release on an average time scale, actin superstructures can be divided into layers or strata based on the enrichment of specific actin–nucleotide complexes or the enriched binding of certain actin-binding proteins. A single actin-binding protein alone can support either an attractive or a repulsive turn. In Xenopus laevis spinal neuronal growth cones, a gradient of bone morphogenetic protein 7 (BMP7) can cause either an attractive or a repulsive turn through the bidirectional phospho-regulation of the actin-binding protein cofilin. Attractive turning requires the activation of a kinase pathway, whereas repulsive turning requires the activation of a Ca 2+ -dependent phosphatase pathway. Thus, actin-binding proteins can function as effective 'signal integrators' of signalling pathways. Distinct but spatially overlapping actin superstructures exist. With the advent of fluorescent speckle microscopy, dynamic characteristics of actin superstructures can be measured and used to identify distinct but spatially overlapping superstructures. In migrating non-neuronal cells, the generation and maintenance of distinct but overlapping superstructures requires the tropomyosin proteins, and although distinct but overlapping superstructures have not been identified in growth cones, all of the required components are pre