The molecular mechanisms of actin regulatory proteins

Actin polymerization is the driving force behind multiple cellular processes including proliferation, motility, adhesion and endocytosis, providing the infrastructure for structural cellular remodeling and intracellular signal transduction. The variety and flexibility of cellular function is achieved by the formation of diverse actin structures. de novo formation of actin filaments is controlled by a combination of G-actin binding proteins, actin severing proteins, and capping factors. In order to overcome these regulatory checkpoints and support efficient actin polymerization, the orchestrated activity of various actin elongation and nucleation proteins, such as formins and the ARP2/3 complex is required. This delicate balance between actin polymerization and de-polymerization must be highly controlled to ensure the formation of the correct actin structures at the correct place and time. The highly controlled actin polymerization process is enabled by the activity of actin nucleation promoting factors (NPFs). These proteins are present in molecular complexes that associate with actin nucleation proteins and are involved in their stabilization and activation at actin-rich sites. These complexes work in concert to control the spatial and temporal formation of diverse actin structures. Recently, the development of cutting-edge imaging technologies have provided new insights into the regulatory mechanisms of the NPFs, and their modes of activation, dynamics and association with the actin nucleation proteins. In this review, we describe the activation mechanisms of actin regulatory proteins, their differential and overlapping functions in actin-dependent processes and structures, and their role in health and disease.