How Actin Assembly Is Modulated at Filament Barbed Ends in Motile Processes

This short review is a survey of the biochemical mechanisms of control of actin filament barbed end assembly in motile processes. Regulated filament treadmilling is at the origin of barbed end growth. Barbed end nucleating, signal-responsive machineries specify the sites of filament assembly at the membrane to elicit polarized migration and determine the number of force-producing filaments. The rate of barbed end growth is controlled both by barbed end-bound factors (leaky cappers, processive motors of actin assembly) and by proteins that associate with monomeric actin and modify the rate of actin association to barbed ends. The flux of assembly at barbed ends of the different complexes of monomeric actin itself is controlled by barbed end capping proteins and by proteins that affect the rate of pointed end depolymerization, which is rate-limiting in the treadmilling cycle. While many actin-binding proteins fulfill one defined regulatory function, some of them can combine two different functions, or switch from one function to the other in a regulated fashion. Understanding the full complexity of motile behavior of living cells requires the biochemical analysis of individual actin regulatory proteins and the development of biomimetic motile systems.