Practice question

Disassembly pathways must balance assembly to allow shape change during migration and division. Cofilin, also called ADF, 15 to 19 kilodalton protein conserved from yeast to mammals, directly severs and depolymerizes actin. Binding preference for ADP F actin, prevalent in older filament regions away from ATP cap, induces 5 degree reduction in helical twist per subunit from 167 to 162 degrees, weakening longitudinal contacts and increasing filament compliance. At boundaries between cofilin decorated and bare segments mechanical stress concentrates leading to breakage. Severing multiplies filament number, creating new barbed ends that can elongate if profilin actin available and pointed ends that depolymerize, increasing turnover. Cofilin activity suppressed by phosphorylation at Ser3 mediated by LIMK downstream of Rho ROCK and PAK signaling, reactivated by slingshot and chronophin phosphatases. Mutations preventing phosphorylation cause loss of stress fibers and exaggerated lamellipodia. Unlike nucleation factors Arp2/3 formin nucleating, unlike thymosin sequestering, cofilin primary role severing and increasing filament turnover essential for motility.