title: Regulation of actin cytoskeleton architecture by Eps8 and Abi1.
abstract: BACKGROUND
  The 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.
  
  
  RESULTS
  Here, 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.
  
  
  CONCLUSIONS
  Together, 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.
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA. roff0013@umn.edu
authors.forename: Julaine
authors.initials: J
authors.lastname: Roffers-Agarwal
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Xanthos
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Miller
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D016764:Cell Polarity; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism*; D000072261:Dishevelled Proteins; D004625:Embryo, Nonmammalian; D004847:Epithelial Cells; D005775:Gastrula; D006801:Humans; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism; D014981:Xenopus; D029867:Xenopus Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: C513733:ABI1 protein, human; C582671:Abi1 protein, Xenopus; C513734:Abi1 protein, mouse; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C000606586:DVL1 protein, Xenopus; D000072261:Dishevelled Proteins; C083430:Eps8 protein, mouse; D010750:Phosphoproteins; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D029867:Xenopus Proteins