Letter abstract
Nature Cell Biology 6, 1180 - 1188 (2004)
Published online: 21 November 2004 | doi:10.1038/ncb1199
Eps8 controls actin-based motility by capping the barbed ends of actin filaments
Andrea Disanza1,2,3,6, Marie-France Carlier3,6, Theresia E. B. Stradal4, Dominique Didry3, Emanuela Frittoli1,2, Stefano Confalonieri1,2, Assunta Croce1,2, Jurgen Wehland4, Pier Paolo Di Fiore1,2,5 & Giorgio Scita1,2
Actin filament barbed-end capping proteins are essential for cell motility, as they regulate the growth of actin filaments to generate propulsive force. One family of capping proteins, whose prototype is gelsolin, shares modular architecture, mechanism of action, and regulation through signalling-dependent mechanisms, such as Ca2+ or phosphatidylinositol-4,5-phosphate binding. Here we show that proteins of another family, the Eps8 family, also show barbed-end capping activity, which resides in their conserved carboxy-terminal effector domain. The isolated effector domain of Eps8 caps barbed ends with an affinity in the nanomolar range. Conversely, full-length Eps8 is auto-inhibited in vitro, and interaction with the Abi1 protein relieves this inhibition. In vivo, Eps8 is recruited to actin dynamic sites, and its removal impairs actin-based propulsion. Eps8-family proteins do not show any similarity to gelsolin-like proteins. Thus, our results identify a new family of actin cappers, and unveil novel modalities of regulation of capping through protein–protein interactions. One established function of the Eps8–Abi1 complex is to participate in the activation of the small GTPase Rac, suggesting a multifaceted role for this complex in actin dynamics, possibly through the participation in alternative larger complexes.
- IFOM Istituto FIRC di Oncologia Molecolare Via Adamello 16, 20139, Milan, Italy.
- Department of Experimental Oncology, Istituto Europeo di Oncologia (IEO), Via Ripamonti 435, 20141, Milan, Italy.
- Dynamique du Cytosquelette Laboratoire d'Enzymologie et Biochimie Structurales, C.N.R.S., 91198 Gif-sur -Yvette, France.
- German Research Centre for Biotechnology (GBF), Department of Cell Biology, Mascheroder Weg 1, D-38124 Braunschweig, Germany.
- Dipartimento di Medicina, Chirurgia ed Odontoiatria, Universita' degli Studi di Milano, 20122 Milan, Italy.
- These authors contributed equally to this work.
Correspondence to: Marie-France Carlier3,6 e-mail: carlier@lebs.cnrs-gif.fr
Correspondence to: Giorgio Scita1,2 e-mail: giorgio.scita@ifom-ieo-campus.it
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
There goes the neighbourhood: Eps8 joins the barbed-end crowdNature Cell Biology News and Views (01 Dec 2004)
Actin assemblyNature News and Views (04 Dec 1980)
See all 4 matches for News And ViewsRESEARCH
The Arp2/3 complex branches filament barbed ends: functional antagonism with capping proteinsNature Cell Biology Article (01 Jul 2000)
Mammalian twinfilin sequesters ADP-G-actin and caps filament barbed ends: implications in motilityThe EMBO Journal Article (22 Mar 2006)
See all 64 matches for Research
