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 Ca(2+) 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.

Eps8 controls actin-based motility by capping the barbed ends of actin filaments / A. Disanza, M.F. Carlier, T.E. Stradal, D. Didry, E. Frittoli, S. Confalonieri, A. Croce, J. Wehland, P.P. Di Fiore, G. Scita. - In: NATURE CELL BIOLOGY. - ISSN 1465-7392. - 6:12(2004 Dec), pp. 1180-1188.

Eps8 controls actin-based motility by capping the barbed ends of actin filaments

P.P. Di Fiore;G. Scita
2004

Abstract

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 Ca(2+) 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.
Cell Movement; Animals; Biological Assay; Mice; Protein Binding; Binding Sites; Fibroblasts; Adaptor Proteins, Signal Transducing; Cells, Cultured; Actins; Proteins; Cytoskeletal Proteins; rac GTP-Binding Proteins; Protein Structure, Tertiary; Polymers; Actin Cytoskeleton
Settore MED/04 - Patologia Generale
dic-2004
Article (author)
File in questo prodotto:
File Dimensione Formato  
ncb1199.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.26 MB
Formato Adobe PDF
1.26 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/33076
Citazioni
  • ???jsp.display-item.citation.pmc??? 97
  • Scopus 162
  • ???jsp.display-item.citation.isi??? 163
social impact