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

Journal Article · · Molecular Biology of the Cell
 [1];  [2];  [3];  [4];  [5];  [6];  [4];  [4];  [5];  [7];  [5]
  1. Univ. of California, San Francisco, CA (United States). Dept. of Cellular and Molecular Pharmacology; DOE/OSTI
  2. Stanford Univ., CA (United States); Univ. of Pittsburgh, PA (United States). Dept. of Cell Biology
  3. Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA (United States). Bioinformatics and Systems Biology Program
  4. Sanford Burnham Medical Research Institute, La Jolla, CA (United States). Bioinformatics and Systems Biology Program
  5. Stanford Univ., CA (United States)
  6. Univ. of Pittsburgh, PA (United States). Dept. of Cell Biology
  7. Univ. of California, San Francisco, CA (United States). Dept. of Cellular and Molecular Pharmacology
+ Show Author Affiliations

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.

Research Organization:
SLAC National Accelerator Laboratory, Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH); March of Dimes
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
1625233
Journal Information:
Molecular Biology of the Cell, Journal Name: Molecular Biology of the Cell Journal Issue: 23 Vol. 24; ISSN 1059-1524
Publisher:
American Society for Cell BiologyCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (28)

Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration journal July 2018
Loss of α-catenin elicits a cholestatic response and impairs liver regeneration journal October 2014
Impaired formation of homotypic cell-in-cell structures in human tumor cells lacking alpha-catenin expression journal July 2015
The role of adherens junction proteins in the regulation of insulin secretion journal March 2018
αT-Catenin Is a Constitutive Actin-binding α-Catenin That Directly Couples the Cadherin·Catenin Complex to Actin Filaments journal July 2016
αT-catenin: A developmentally dispensable, disease-linked member of the α-catenin family journal April 2018
The formation of ordered nanoclusters controls cadherin anchoring to actin and cell–cell contact fluidity journal July 2015
Reevaluating αE-catenin monomer and homodimer functions by characterizing E-cadherin/αE-catenin chimeras journal September 2015
NF2/Merlin mediates contact-dependent inhibition of EGFR mobility and internalization via cortical actomyosin journal October 2015
α-Catenin homodimers are recruited to phosphoinositide-activated membranes to promote adhesion journal September 2017
Characterization of the Cadherin–Catenin Complex of the Sea Anemone Nematostella vectensis and Implications for the Evolution of Metazoan Cell–Cell Adhesion journal April 2016
Steric Regulation of Tandem Calponin Homology Domain Actin-Binding Affinity posted_content October 2019
Telophase correction refines division orientation in stratified epithelia posted_content June 2019
Switching of α-Catenin From Epithelial to Neuronal Type During Lens Epithelial Cell Differentiation journal July 2017
Force Dependent Biotinylation of Myosin IIA by α-Catenin Tagged with a Promiscuous Biotin Ligase journal March 2015
Measuring Protein Binding to F-actin by Co-sedimentation
  • J., Dickinson, Daniel; A., Heier, Jonathon; V., Kwiatkowski, Adam
  • The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/6xb2-3t98
text January 2017
Force-dependent conformational switch of α-catenin controls vinculin binding journal July 2014
Beyond β-catenin: prospects for a larger catenin network in the nucleus journal November 2015
Dynamic contacts: rearranging adherens junctions to drive epithelial remodelling journal May 2014
Force-dependent allostery of the α-catenin actin-binding domain controls adherens junction dynamics and functions journal November 2018
Rho GTPases and the Downstream Effectors Actin-related Protein 2/3 (Arp2/3) Complex and Myosin II Induce Membrane Fusion at Self-contacts journal February 2015
α-Catenin–mediated cadherin clustering couples cadherin and actin dynamics journal August 2015
Steric regulation of tandem calponin homology domain actin-binding affinity journal December 2019
Actin-Based Adhesion Modules Mediate Cell Interactions with the Extracellular Matrix and Neighboring Cells journal July 2017
Integration of Cadherin Adhesion and Cytoskeleton at Adherens Junctions journal January 2017
The minimal cadherin-catenin complex binds to actin filaments under force journal October 2014
Proximity biotinylation provides insight into the molecular composition of focal adhesions at the nanometer scale journal June 2016
Telophase correction refines division orientation in stratified epithelia journal December 2019

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