FMNL2 drives actin-based protrusion and migration downstream of Cdc42

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Jennifer Block
  • Dennis Breitsprecher
  • Sonja Kühn
  • Moritz Winterhoff
  • Frieda Kage
  • Robert Geffers
  • Patrick Duwe
  • Jennifer L Rohn
  • Buzz Baum
  • Brakebusch, Cord Herbert
  • Matthias Geyer
  • Theresia E B Stradal
  • Jan Faix
  • Klemens Rottner
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.
OriginalsprogEngelsk
TidsskriftCurrent Biology
Vol/bind22
Udgave nummer11
Sider (fra-til)1005-12
Antal sider8
ISSN0960-9822
DOI
StatusUdgivet - 5 jun. 2012

ID: 40299548