Article
- The EMBO Journal (2006) 25, 1184 - 1195
- doi:10.1038/sj.emboj.7601019
Published online: 2 March 2006
Subject Category:
Mammalian twinfilin sequesters ADP-G-actin and caps filament barbed ends: implications in motility
Emmanuèle Helfer1,a, Elisa M Nevalainen2,a, Perttu Naumanen2, Stéphane Romero1, Dominique Didry1, Dominique Pantaloni1, Pekka Lappalainen2 and Marie-France Carlier1
- Cytoskeleton Dynamics and Motility, LEBS, CNRS, Gif-sur-Yvette, France
- Institute of Biotechnology, University of Helsinki, Finland
Correspondence to:
Marie-France Carlier, Dynamique du Cytosquelette, LEBS, CNRS, Gif-sur-Yvette F-91198, France. Tel.: +33 1 69 82 34 65; Fax: +33 1 69 82 341 29; E-mail: carlier@lebs.cnrs-gif.fr
Pekka Lappalainen, Institute of Biotechnology, University of Helsinki, Finland. Tel.: +358 9 191 59499; E-mail: Pelappal@operoni.helsinki.fi
aThese authors equally contributed to the work
Received 30 June 2005; Accepted 2 February 2006
Abstract
Twinfilins are conserved actin-binding proteins composed of two actin depolymerizing factor homology (ADF-H) domains. Twinfilins are involved in diverse morphological and motile processes, but their mechanism of action has not been elucidated. Here, we show that mammalian twinfilin both sequesters ADP-G-actin and caps filament barbed ends with preferential affinity for ADP-bound ends. Twinfilin replaces capping protein and promotes motility of N-WASP functionalized beads in a biomimetic motility assay, indicating that the capping activity supports twinfilin's function in motility. Consistently, in vivo twinfilin localizes to actin tails of propelling endosomes. The ADP-actin-sequestering activity cooperates with the filament capping activity of twinfilin to finely regulate motility due to processive filament assembly catalyzed by formin-functionalized beads. The isolated ADF-H domains do not cap barbed ends nor promote motility, but sequester ADP-actin, the C-terminal domain showing the highest affinity. A structural model for binding of twinfilin to barbed ends is proposed based on the similar foldings of twinfilin ADF-H domains and gelsolin segments.
Keywords:
- actin,
- ADF homology domains,
- capping proteins,
- motility,
- twinfilin
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