Filopodia: The Fingers That Do the Walking

Filopodia are actin-based structures composed of parallel bundles of actin filaments and various actin-associated proteins, and they play important roles in cell-cell signaling, guidance toward chemoattractants, and adhesion to the extracellular matrix. Two mechanisms for the formation of filopodia have been suggested, each using different sets of actin-regulating proteins, creating some controversy in the field. New molecules, some of unknown functions, have also been implicated in filopodium formation, suggesting that other possible mechanisms of filopodium formation exist. We discuss established and novel proteins that mediate the formation and dynamics of filopodia, different mechanisms of filopodium formation, and the various functions that distinct filopodia perform. The actin cytoskeleton is regulated by a vast number of proteins that modulate the types of actin-based structures formed in the cell. The filopodium, one such actin-based structure, is composed of bundles of parallel, filamentous actin that extend from the edge of the cell and is thought to act as a sensor of the extracellular environment. Filopodia are involved in many cellular functions, including cell-cell signaling, cell migration toward extracellular guidance factors, and adhesion to the extracellular environment. Several of the molecules that modulate the actin cytoskeleton, such as the Arp2/3 (actin-related protein 2 and 3) complex, Enabled (Ena)/VASP (vasodilator-stimulated phosphoprotein) proteins, Dia2, and fascin, have been implicated in filopodium formation, leading to two proposed mechanisms of filopodium formation. However, with progress in the field and the identification of several new molecular players that stimulate filopodium formation, the possible mechanisms involved need to be reevaluated. We review established and novel molecules involved in filopodium formation and dynamics and discuss possible mechanisms of filopodium formation and the possible functions that filopodia formed by distinct mechanisms may play in different cell types.