Importance of free actin filament barbed ends for Arp2/3 complex function in platelets and fibroblasts

被引:68
作者
Falet, H
Hoffmeister, KM
Neujahr, R
Italiano, JE
Stossel, TP
Southwick, FS
Hartwig, JH
机构
[1] Harvard Univ, Sch Med, Div Hematol, Brigham & Womens Hosp,Dept Med, Boston, MA 02115 USA
[2] Univ Florida, Div Infect Dis, Dept Med, Coll Med, Gainesville, FL 32610 USA
关键词
D O I
10.1073/pnas.222652499
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We investigated the effect of actin filament barbed end uncapping on Arp2/3 complex function both in vivo and in vitro. Arp2/3 complex redistributes rapidly and uniformly to the lamellar edge of activated wild-type platelets and fibroblasts but clusters in marginal actin filament clumps in gelsolin-null cells. Treatment of gelsolin-null platelets with the negative dominant N-WASp C-terminal CA domain has no effect on their residual actin nucleation activity, placing gelsolin actin filament severing, capping, and uncapping function upstream of Arp2/3 complex nucleation. Actin filaments capped by gelsolin or the gelsolin homolog CapG fail to enhance Arp2/3 complex nucleation in vitro, but uncapping of the barbed ends of these actin filaments restores their ability to potentiate Arp2/3 complex nucleation. We conclude that Arp2/3 complex contribution to actin filament nucleation in platelets and fibroblasts importantly requires free barbed ends generated by severing and uncapping.
引用
收藏
页码:16782 / 16787
页数:6
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