Open AccessSynergy between Cyclase-associated protein and Cofilin accelerates actin filament depolymerization by two orders of magnitude
Author(s) -
Shashank Shekhar,
Johnson Chung,
Jané Kondev,
Jeff Gelles,
Bruce L. Goode
Publication year - 2019
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/s41467-019-13268-1
Subject(s) - cofilin , protein filament , depolymerization , actin , actin remodeling , microbiology and biotechnology , biophysics , actin remodeling of neurons , actin binding protein , mdia1 , chemistry , cytoskeleton , actin cytoskeleton , biology , biochemistry , cell , organic chemistry
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.