Mechanism of the cadherin–catenin F-actin catch bond interaction
- Stanford Univ., CA (United States)
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
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