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FMNL2 drives actin-based protrusion and migration downstream of Cdc42.
- Source :
-
Current biology : CB [Curr Biol] 2012 Jun 05; Vol. 22 (11), pp. 1005-12. Date of Electronic Publication: 2012 May 17. - Publication Year :
- 2012
-
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.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1879-0445
- Volume :
- 22
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Current biology : CB
- Publication Type :
- Academic Journal
- Accession number :
- 22608513
- Full Text :
- https://doi.org/10.1016/j.cub.2012.03.064