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

Block, J; Breitsprecher, D; Kühn, S; Winterhoff, M; Kage, F; Geffers, R; Duwe, P; ... Rottner, K; + view all (2012) FMNL2 drives actin-based protrusion and migration downstream of Cdc42. Curr Biol , 22 (11) 1005 - 1012. 10.1016/j.cub.2012.03.064. Green open access

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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.

Type: Article
Title: FMNL2 drives actin-based protrusion and migration downstream of Cdc42.
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cub.2012.03.064
Publisher version: http://dx.doi.org/10.1016/j.cub.2012.03.064
Language: English
Additional information: © 2012 Elsevier Ltd All rights reserved. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. PMCID: PMC3765947
Keywords: Actin Cytoskeleton, Actins, Animals, Cell Movement, HeLa Cells, Humans, Mice, NIH 3T3 Cells, Polymerization, Proteins, Pseudopodia, Signal Transduction, cdc42 GTP-Binding Protein
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1357989
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