Synergy between Cyclase-associated protein and Cofilin accelerates actin filament depolymerization by two orders of magnitude.

Shashank Shekhar, Johnson Chung, Jane Kondev, Jeff Gelles, Bruce L Goode

Nature communications 2019 Nov 22

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Cellular actin networks can be rapidly disassembled and remodeled in a few seconds, yet in vitro actin filaments depolymerize slowly over minutes. The cellular mechanisms enabling actin to depolymerize this fast have so far remained obscure. Using microfluidics-assisted TIRF, we show that Cyclase-associated protein (CAP) and Cofilin synergize to processively depolymerize actin filament pointed ends at a rate 330-fold faster than spontaneous depolymerization. Single molecule imaging further reveals that hexameric CAP molecules interact with the pointed ends of Cofilin-decorated filaments for several seconds at a time, removing approximately 100 actin subunits per binding event. These findings establish a paradigm, in which a filament end-binding protein and a side-binding protein work in concert to control actin dynamics, and help explain how rapid actin network depolymerization is achieved in cells.

Citation

Shashank Shekhar, Johnson Chung, Jane Kondev, Jeff Gelles, Bruce L Goode. Synergy between Cyclase-associated protein and Cofilin accelerates actin filament depolymerization by two orders of magnitude. Nature communications. 2019 Nov 22;10(1):5319