Abstract
BackgroundThe actin cytoskeleton participates in many fundamental processes including the regulation of cell shape, motility, and adhesion. The remodeling of the actin cytoskeleton is dependent on actin binding proteins, which organize actin filaments into specific structures that allow them to perform various specialized functions. The Eps8 family of proteins is implicated in the regulation of actin cytoskeleton remodeling during cell migration, yet the precise mechanism by which Eps8 regulates actin organization and remodeling remains elusive.ResultsHere, we show that Eps8 promotes the assembly of actin rich filopodia-like structures and actin cables in cultured mammalian cells and Xenopus embryos, respectively. The morphology of actin structures induced by Eps8 was modulated by interactions with Abi1, which stimulated formation of actin cables in cultured cells and star-like structures in Xenopus. The actin stars observed in Xenopus animal cap cells assembled at the apical surface of epithelial cells in a Rac-independent manner and their formation was accompanied by recruitment of N-WASP, suggesting that the Eps8/Abi1 complex is capable of regulating the localization and/or activity of actin nucleators. We also found that Eps8 recruits Dishevelled to the plasma membrane and actin filaments suggesting that Eps8 might participate in non-canonical Wnt/Polarity signaling. Consistent with this idea, mis-expression of Eps8 in dorsal regions of Xenopus embryos resulted in gastrulation defects.ConclusionTogether, these results suggest that Eps8 plays multiple roles in modulating actin filament organization, possibly through its interaction with distinct sets of actin regulatory complexes. Furthermore, the finding that Eps8 interacts with Dsh and induced gastrulation defects provides evidence that Eps8 might participate in non-canonical Wnt signaling to control cell movements during vertebrate development.
Highlights
The actin cytoskeleton participates in many fundamental processes including the regulation of cell shape, motility, and adhesion
Eps8 can bind to both barbed ends and the sides of actin filaments [9,10] and it is possible that these different modes of actin binding mediate distinct effects on actin architecture in cells
Barbed-end capping activity might regulate actin filament dynamics and stabilize existing filaments whereas an alternative activity might promote the formation and maintenance of actin arrays required for protrusive force generation and cellular structures such as microvilli and filopodia
Summary
The actin cytoskeleton participates in many fundamental processes including the regulation of cell shape, motility, and adhesion. Actin organization is regulated by growth factor signals that stimulate the activity of Rho family GTPases, which mediate actin remodeling and formation of stress fibers, filopodia, and membrane ruffles [2]. Eps is thought to transduce growth factor signals by acting as a scaffold protein to support the formation of multi-protein signaling complexes that promote the activation of Rho family GTPases. Consistent with this model, studies in Eps null fibroblasts showed that Eps is required for growth factor-induced Rac activation as well as Racdependent actin remodeling and membrane ruffling [6]. Eps interacts directly with Abi through its SH3 domain, which possesses a novel peptide binding specificity [8], and this binding is thought to relieve auto-inhibition of Eps8 [9]
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