HUMAN ACTIN DEPOLYMERIZING FACTOR MEDIATES A PH-SENSITIVE DESTRUCTIONOF ACTIN-FILAMENTS

ADF (actin depolymerizing factor) is an M(r) 19 000 actin-binding prot ein present in many vertebrate tissues and particularly abundant in ne uronal cells. We have cloned human ADF and here show it to be identica l in sequence to porcine destrin. Human ADF expressed in Escherichia c oli behaves like native ADF from porcine brain. It binds to G-actin at pH 8 with a 1:1 stoichiometry and K(d) approximately 0.2 muM, thereby sequestering monomers and preventing polymerization. It does not cose diment with F-actin at this pH, but severs actin filaments in a calciu m-insensitive manner. The severing activity is only about 0.1% efficie nt. By contrast, at pH values below 7, ADF binds to actin filaments in a highly cooperative manner and at a 1:1 ratio to filament subunits. When the pH is raised to 8.0, the decorated filaments are rapidly seve red and depolymerized.