FMNL2 drives actin-based protrusion and migration downstream of Cdc42.

Autor:	Block J; Institute of Genetics, University of Bonn, Karlrobert-Kreiten-Strasse 13, 53115 Bonn, Germany., Breitsprecher D, Kühn S, Winterhoff M, Kage F, Geffers R, Duwe P, Rohn JL, Baum B, Brakebusch C, Geyer M, Stradal TE, Faix J, Rottner K
Jazyk:	angličtina
Zdroj:	Current biology : CB [Curr Biol] 2012 Jun 05; Vol. 22 (11), pp. 1005-12. Date of Electronic Publication: 2012 May 17.
DOI:	10.1016/j.cub.2012.03.064
Abstrakt:	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. (Copyright © 2012 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu