The ADF/cofilin proteins: stimulus-responsive modulators of actin dynamics.

Whether a cell is harnessing actin polymerization to produce movement, preparing for cytokinesis, or assembling long-lived actin filament-based structures such as sarcomeres or microvilli, actin polymerization must be controlled in time and space. Changes in actin organization often occur on a time scale that dictates an intimate coupling of a signal transduction apparatus to the machinery that controls actin assembly. This is the case when a motile cell extends pseudopodia in the direction of a gradient of increasing chemoattractant. To mediate such responses, eukaryotic cells are equipped with a battery of actin-binding proteins (Stossel et al., 1985; Pollard and Cooper, 1986). Several lines of evidence have now converged to implicate the ADF/cofilin proteins in particular as stimulus-responsive mediators of actin dynamics. The ADF/cofilins are endowed with multiple activities that can modulate assembly, and these activities are inhibited by a phosphorylation that occurs in vivo. Significantly, ADF/cofilins undergo rapid dephosphorylation when cells are exposed to stimuli that cause changes in cytoskeletal assembly. Additional regulatory possibilities are suggested by observations that the actions and activities of ADF/cofilins can be influenced by pH, PIP2, the nature of the actin filament-bound nucleotide (ATP or ADP), inorganic phosphate, and possibly, translocation into the nucleus and tension on the actin filament.