αE-catenin actin-binding domain alters actin filament conformation and regulates binding of nucleation and disassembly factors

Mol Biol Cell. 2013 Dec;24(23):3710-20. doi: 10.1091/mbc.E13-07-0388. Epub 2013 Sep 25.

Abstract

The actin-binding protein αE-catenin may contribute to transitions between cell migration and cell-cell adhesion that depend on remodeling the actin cytoskeleton, but the underlying mechanisms are unknown. We show that the αE-catenin actin-binding domain (ABD) binds cooperatively to individual actin filaments and that binding is accompanied by a conformational change in the actin protomer that affects filament structure. αE-catenin ABD binding limits barbed-end growth, especially in actin filament bundles. αE-catenin ABD inhibits actin filament branching by the Arp2/3 complex and severing by cofilin, both of which contact regions of the actin protomer that are structurally altered by αE-catenin ABD binding. In epithelial cells, there is little correlation between the distribution of αE-catenin and the Arp2/3 complex at developing cell-cell contacts. Our results indicate that αE-catenin binding to filamentous actin favors assembly of unbranched filament bundles that are protected from severing over more dynamic, branched filament arrays.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actin Cytoskeleton / ultrastructure
  • Actin Depolymerizing Factors / metabolism
  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / metabolism*
  • Animals
  • Cryoelectron Microscopy
  • Dogs
  • Image Processing, Computer-Assisted
  • Madin Darby Canine Kidney Cells
  • Mice
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Tertiary
  • Structure-Activity Relationship
  • alpha Catenin / chemistry*
  • alpha Catenin / metabolism*

Substances

  • Actin Depolymerizing Factors
  • Actin-Related Protein 2-3 Complex
  • Actins
  • alpha Catenin