Instantaneous inactivation of cofilin reveals its function of F-actin disassembly in lamellipodia

被引:38
作者
Vitriol, Eric A. [1 ,2 ]
Wise, Ariel L. [1 ,2 ]
Berginski, Mathew E. [3 ]
Bamburg, James R. [4 ]
Zheng, James Q. [1 ,2 ]
机构
[1] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Dept Cell Biol, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Dept Neurol, Atlanta, GA 30322 USA
[3] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27599 USA
[4] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA
基金
美国国家卫生研究院;
关键词
ASSISTED LASER INACTIVATION; EGFP-FUSION PROTEINS; DEPOLYMERIZING FACTOR; FILAMENT TURNOVER; ARP2/3; COMPLEX; NUCLEOTIDE STATE; LINKED CHANGES; CELL BIOLOGY; ADF/COFILIN; NUCLEATION;
D O I
10.1091/mbc.E13-03-0156
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:2238 / 2247
页数:10
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