Renaissance at the actin filament pointed end: Mechanisms of assembly, capping and depolymerization

Cellular and biochemical studies of actin assembly have long focused primarily on reactions at the fast-growing barbed end of actin filaments. In contrast, the slow-growing pointed end has traditionally received comparatively less attention. Recent structural, biochemical, and cell biological studies have sparked a renaissance in pointed-end research, revealing its active roles in both actin assembly and disassembly. The discovery of the pointed end polymerase activity of the bacterial effector VopF has challenged barbed-end centric assembly paradigms and reinvigorated efforts to identify endogenous pointed-end elongators. This review highlights the emerging molecular machinery and mechanisms governing pointed-end dynamics, including nucleation, elongation, capping, and disassembly. We discuss the physiological significance of pointed-end regulation and argue that a comprehensive understanding of actin regulation requires close attention to pointed end dynamics.