Filamentous actin (F-actin) (F-actin)

Filamentous actin (F-actin) is a polar, helical polymer composed of globular actin (G-actin) subunits, serving as a fundamental component of the eukaryotic cytoskeleton [1, 2]. It is characterized by two distinct ends: the fast-growing "barbed" (plus) end and the slower-growing "pointed" (minus) end, with dynamics regulated by a suite of actin-binding proteins [3, 7]. F-actin is essential for critical cellular processes, including the maintenance of cell shape, muscle contraction, cytokinesis, and motility through the formation of lamellipodia and filopodia [2, 8]. In pathological states, actin dynamics are often hijacked; for instance, cancer cells utilize actin remodeling for metastasis and invasion, while various pathogens exploit the host's actin machinery for intracellular movement [14, 18]. The barbed end is a primary regulatory site where many actin-binding proteins and drugs, such as cytochalasins, exert their effects to control polymerization [1, 29]. While its ubiquitous presence in all eukaryotic cells makes systemic therapeutic targeting challenging due to severe toxicity, F-actin and its barbed ends are targets for various natural toxins and are being investigated for localized treatments [15, 16]. For example, latrunculin B has been explored in clinical trials for the treatment of glaucoma by modulating trabecular meshwork outflow [21, 24]. Overall, F-actin remains a vital target for understanding cellular mechanics and developing site-specific therapeutic strategies [14, 39].

Other names

Actin filamentMicrofilamentBarbed endPlus end of actinActin polymer

Drugs target F-actin by either binding to the barbed end to inhibit monomer addition and dissociation (e.g., cytochalasins), stabilizing the filament structure to prevent depolymerization (e.g., phalloidin, jasplakinolide), or sequestering G-actin monomers to indirectly promote filament disassembly (e.g., latrunculins).