FMNL2 drives actin-based protrusion and migration downstream of Cdc42

Research output: Contribution to journalJournal articleResearchpeer-review

  • 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.
Original languageEnglish
JournalCurrent Biology
Volume22
Issue number11
Pages (from-to)1005-12
Number of pages8
ISSN0960-9822
DOIs
Publication statusPublished - 5 Jun 2012

ID: 40299548