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Title: Mechanism of the cadherin–catenin F-actin catch bond interaction

Journal Article · · eLife
DOI:https://doi.org/10.7554/elife.80130· OSTI ID:1983349

Mechanotransduction at cell–cell adhesions is crucial for the structural integrity, organization, and morphogenesis of epithelia. At cell–cell junctions, ternary E-cadherin/β-catenin/αE-catenin complexes sense and transmit mechanical load by binding to F-actin. The interaction with F-actin, described as a two-state catch bond, is weak in solution but is strengthened by applied force due to force-dependent transitions between weak and strong actin-binding states. Here, we provide direct evidence from optical trapping experiments that the catch bond property principally resides in the αE-catenin actin-binding domain (ABD). Consistent with our previously proposed model, the deletion of the first helix of the five-helix ABD bundle enables stable interactions with F-actin under minimal load that are well described by a single-state slip bond, even when αE-catenin is complexed with β-catenin and E-cadherin. Our data argue for a conserved catch bond mechanism for adhesion proteins with structurally similar ABDs. We also demonstrate that a stably bound ABD strengthens load-dependent binding interactions between a neighboring complex and F-actin, but the presence of the other αE-catenin domains weakens this effect. These results provide mechanistic insight to the cooperative binding of the cadherin–catenin complex to F-actin, which regulate dynamic cytoskeletal linkages in epithelial tissues.

Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); National Science Foundation (NSF)
Grant/Contract Number:
AC02-76SF00515; R01GM114462; R35GM130332; R35GM131747; T32GM120007; P30GM133894
OSTI ID:
1983349
Journal Information:
eLife, Vol. 11; ISSN 2050-084X
Publisher:
eLife Sciences Publications, Ltd.Copyright Statement
Country of Publication:
United States
Language:
English

References (48)

Estimating the Dimension of a Model journal March 1978
Actin and Actin-Binding Proteins journal March 2016
Mechanobiology of collective cell behaviours journal November 2017
α-Catenin as a tension transducer that induces adherens junction development journal May 2010
The Actin Cytoskeleton and Actin-Based Motility journal January 2018
Vinculin regulates directionality and cell polarity in two- and three-dimensional matrix and three-dimensional microtrack migration journal May 2016
α-catenin switches between a slip and an asymmetric catch bond with F-actin to cooperatively regulate cell junction fluidity journal March 2022
Dynamics of unbinding of cell adhesion molecules: Transition from catch to slip bonds journal February 2005
Force-dependent allostery of the α-catenin actin-binding domain controls adherens junction dynamics and functions journal November 2018
The minimal cadherin-catenin complex binds to actin filaments under force journal October 2014
An Autoinhibited Structure of α-Catenin and Its Implications for Vinculin Recruitment to Adherens Junctions journal April 2013
Intrasteric Inhibition Mediates the Interaction of the I/LWEQ Module Proteins Talin1, Talin2, Hip1, and Hip12 with Actin journal November 2004
Structure and Biochemistry of Cadherins and Catenins journal August 2009
Binding partner- and force-promoted changes in αE-catenin conformation probed by native cysteine labeling journal October 2019
Actin-based force generation and cell adhesion in tissue morphogenesis journal May 2021
Catch-Bond Model Derived from Allostery Explains Force-Activated Bacterial Adhesion journal February 2006
α-Catenin Structure and Nanoscale Dynamics in Solution and in Complex with F-Actin journal August 2018
Genome remodelling in a basal-like breast cancer metastasis and xenograft journal April 2010
Structural definition of the F-actin–binding THATCH domain from HIP1R journal January 2006
The Structural Basis of Actin Organization by Vinculin and Metavinculin journal January 2016
Molecular mechanism for direct actin force-sensing by α-catenin journal September 2020
Power spectrum analysis for optical tweezers journal March 2004
Monomeric α-catenin links cadherin to the actin cytoskeleton journal February 2013
Vinculin forms a directionally asymmetric catch bond with F-actin journal August 2017
Structure of the Dimerization and β-Catenin- Binding Region of α-Catenin journal March 2000
UCSF Chimera?A visualization system for exploratory research and analysis journal January 2004
Force-dependent conformational switch of α-catenin controls vinculin binding journal July 2014
 E-catenin is an autoinhibited molecule that coactivates vinculin journal May 2012
Mechanical regulation of tension-transmission supramolecular linkages journal February 2021
αE-catenin actin-binding domain alters actin filament conformation and regulates binding of nucleation and disassembly factors journal December 2013
Danio rerio αE-catenin Is a Monomeric F-actin Binding Protein with Distinct Properties from Mus musculus αE-catenin journal June 2013
Adherens Junction: Molecular Architecture and Regulation journal August 2009
A new look at the statistical model identification journal December 1974
The structure of the C-terminal actin-binding domain of talin journal December 2007
Structural basis of αE-catenin–F-actin catch bond behavior journal September 2020
Dynamic strength of molecular adhesion bonds journal April 1997
Mechano-adaptive sensory mechanism of α-catenin under tension journal April 2016
The C-terminal actin-binding domain of talin forms an asymmetric catch bond with F-actin journal March 2022
α-Catenin Is a Molecular Switch that Binds E-Cadherin-β-Catenin and Regulates Actin-Filament Assembly journal December 2005
Deconstructing the Cadherin-Catenin-Actin Complex journal December 2005
Dimer asymmetry defines α-catenin interactions journal January 2013
Structural and Thermodynamic Characterization of Cadherin·β-Catenin·α-Catenin Complex Formation journal April 2014
Models for the specific adhesion of cells to cells journal May 1978
Tensile Forces and Mechanotransduction at Cell–Cell Junctions journal April 2018
tweezercalib 2.1: Faster version of MatLab package for precise calibration of optical tweezers journal October 2006
Phenomenological and microscopic theories for catch bonds journal January 2017
Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II–dependent manner journal June 2010
Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex. journal September 1995