FMNL2 Drives Actin-Based Protrusion and Migration Downstream of Cdc42

被引：158

作者：

Block, Jennifer ^{[1
]}

Breitsprecher, Dennis ^{[2
]}

Kuehn, Sonja ^{[3
]}

Winterhoff, Moritz ^{[2
]}

Kage, Frieda ^{[1
]}

Geffers, Robert ^{[4
]}

Duwe, Patrick ^{[5
]}

Rohn, Jennifer L. ^{[6
]}

Baum, Buzz ^{[6
]}

Brakebusch, Cord ^{[7
]}

Geyer, Matthias ^{[3
]}

Stradal, Theresia E. B. ^{[4
,5
]}

Faix, Jan ^{[2
]}

Rottner, Klemens ^{[1
,4
]}

机构：

[1] Univ Bonn, Inst Genet, D-53115 Bonn, Germany

[2] Hannover Med Sch, Inst Biophys Chem, D-30623 Hannover, Germany

[3] Max Planck Inst Mol Physiol, D-44227 Dortmund, Germany

[4] Helmholtz Ctr Infect Res, D-38124 Braunschweig, Germany

[5] Univ Munster, Inst Mol Cell Biol, D-48149 Munster, Germany

[6] UCL, MRC Lab Mol Cell Biol, London WC1E 6BT, England

[7] Univ Copenhagen, BRIC, DK-2200 Copenhagen, Denmark

来源：

CURRENT BIOLOGY | 2012年 / 22卷 / 11期

关键词：

FILOPODIUM FORMATION; LAMELLIPODIA; COMPLEX; FORMIN; RAC; PROFILIN; CELLS; MDIA2; FRL2; WAVE;

D O I：

10.1016/j.cub.2012.03.064

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cell migration entails protrusion of lamellipodia, densely packed networks of actin filaments at the cell front. Filaments are generated by nucleation, likely mediated by Arp2/3 complex and its activator Scar/WAVE [1]. It is unclear whether formins contribute to lamellipodial actin filament nucleation or serve as elongators of filaments nucleated by Arp2/3 complex [2]. Here we show that the Diaphanous-related formin FMNL2, also known as FRL3 or FHOD2 [3], accumulates at lamellipodia and filopodia tips. FMNL2 is cotranslationally modified by myristoylation and regulated by interaction with the Rho-guanosine triphosphatase Cdc42. Abolition of myristoylation or Cdc42 binding interferes with proper FMNL2 activation, constituting an essential prerequisite for subcellular targeting. In vitro, C-terminal FMNL2 drives elongation rather than nucleation of actin filaments in the presence of profilin. In addition, filament ends generated by Arp2/3-mediated branching are captured and efficiently elongated by the formin. Consistent with these biochemical properties, RNAi-mediated silencing of FMNL2 expression decreases the rate of lamellipodia protrusion and, accordingly, the efficiency of cell migration. Our data establish that the FMNL subfamily member FMNL2 is a novel elongation factor of actin filaments that constitutes the first Cdc42 effector promoting cell migration and actin polymerization at the tips of lamellipodia.

引用

页码：1005 / 1012

页数：8

共 34 条

[1] The cool-2/α-Pix protein mediates a Cdc42-Rac signaling cascade [J].