Eps8 controls actin-based motility by capping the barbed ends of actin filaments.
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.
Disanza
Andrea
A
IFOM Istituto FIRC di Oncologia Molecolare Via Adamello 16, 20139, Milan, Italy.
Carlier
Marie-France
MF
Stradal
Theresia E B
TE
Didry
Dominique
D
Frittoli
Emanuela
E
Confalonieri
Stefano
S
Croce
Assunta
A
Wehland
Jurgen
J
Di Fiore
Pier Paolo
PP
Scita
Giorgio
G
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000096:biosynthesis / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001681:Biological Assay; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology; D051379:Mice; D011108:Polymers / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011506:Proteins / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
C513734:Abi1 protein, mouse; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C083430:Eps8 protein, mouse; D011108:Polymers; D011506:Proteins; D020744:rac GTP-Binding Proteins