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FMNL2 drives actin-based protrusion and migration downstream of Cdc42.
Block, Jennifer Breitsprecher, Dennis Kühn, Sonja Winterhoff, Moritz Kage, Frieda Geffers, Robert Duwe, Patrick Rohn, Jennifer L Baum, Buzz Brakebusch, Cord
Block, Jennifer
Breitsprecher, Dennis
Kühn, Sonja
Winterhoff, Moritz
Kage, Frieda
Geffers, Robert
Duwe, Patrick
Rohn, Jennifer L
Baum, Buzz
Brakebusch, Cord
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2012-06-05
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Abstract
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. It is unclear whether formins contribute to lamellipodial actin filament nucleation or serve as elongators of filaments nucleated by Arp2/3 complex. Here we show that the Diaphanous-related formin FMNL2, also known as FRL3 or FHOD2, 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.
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FMNL2 drives actin-based protrusion and migration downstream of Cdc42. 2012, 22 (11):1005-12 Curr. Biol.
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en
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1879-0445
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Archived with thanks to Current biology : CB