TY - JOUR
T1 - Instantaneous inactivation of cofilin reveals its function of F-actin disassembly in lamellipodia
AU - Vitriol, Eric A.
AU - Wise, Ariel L.
AU - Berginski, Mathew E.
AU - Bamburg, James R.
AU - Zheng, James Q.
PY - 2013/7/15
Y1 - 2013/7/15
N2 - Cofilin is a key regulator of the actin cytoskeleton. It can sever actin filaments, accelerate filament disassembly, act as a nucleation factor, recruit or antagonize other actin regulators, and control the pool of polymerization-competent actin monomers. In cells these actions have complex functional outputs. The timing and localization of cofilin activity are carefully regulated, and thus global, long-term perturbations may not be sufficient to probe its precise function. To better understand cofilin's spatiotemporal action in cells, we implemented chromophore-assisted laser inactivation (CALI) to instantly and specifically inactivate it. In addition to globally inhibiting actin turnover, CALI of cofilin generated several profound effects on the lamellipodia, including an increase of F-actin, a rearward expansion of the actin network, and a reduction in retrograde flow speed. These results support the hypothesis that the principal role of cofilin in lamellipodia at steady state is to break down F-actin, control filament turnover, and regulate the rate of retrograde flow.
AB - Cofilin is a key regulator of the actin cytoskeleton. It can sever actin filaments, accelerate filament disassembly, act as a nucleation factor, recruit or antagonize other actin regulators, and control the pool of polymerization-competent actin monomers. In cells these actions have complex functional outputs. The timing and localization of cofilin activity are carefully regulated, and thus global, long-term perturbations may not be sufficient to probe its precise function. To better understand cofilin's spatiotemporal action in cells, we implemented chromophore-assisted laser inactivation (CALI) to instantly and specifically inactivate it. In addition to globally inhibiting actin turnover, CALI of cofilin generated several profound effects on the lamellipodia, including an increase of F-actin, a rearward expansion of the actin network, and a reduction in retrograde flow speed. These results support the hypothesis that the principal role of cofilin in lamellipodia at steady state is to break down F-actin, control filament turnover, and regulate the rate of retrograde flow.
UR - http://www.scopus.com/inward/record.url?scp=84880411148&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880411148&partnerID=8YFLogxK
U2 - 10.1091/mbc.E13-03-0156
DO - 10.1091/mbc.E13-03-0156
M3 - Article
C2 - 23676663
AN - SCOPUS:84880411148
SN - 1059-1524
VL - 24
SP - 2238
EP - 2247
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 14
ER -