Structural and Thermodynamic Characterization of Cadherin·β-Catenin·α-Catenin Complex Formation

Pokutta, Sabine; Choi, Hee Jung; Ahlsén, Göran; Hansen, Scott D.; Weis, William I.

doi:10.1074/jbc.m114.554709

Cited by 55 publications

(103 citation statements)

References 48 publications

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“…3 VE-cadherin expression on the plasma membrane is promoted and stabilized by the expression of cytoplasmic adaptor proteins p120-catenin and b¡catenin which bind to the juxtamembrane and C-terminal portion of the VE-cadherin cytoplasmic domain, respectively. b¡catenin also mediates the connection between VE-cadherin and the actin cytoskeleton via adaptor proteins such as a¡catenin 4,5 ; this connection is absolutely required for junction maintenance. In addition, VE-cadherin adhesion is regulated by actin cytoskeletal dynamics.…”

Section: Regulation Of Inter-endothelial Adherens Junctions Under Resmentioning

confidence: 99%

Control of vascular permeability by adhesion molecules

Sarelius

Glading²

2014

Tissue Barriers

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Vascular permeability is a vital function of the circulatory system that is regulated in large part by the limited flux of solutes, water, and cells through the endothelial cell layer. One major pathway through this barrier is via the inter-endothelial junction, which is driven by the regulation of cadherin-based adhesions. The endothelium also forms attachments with surrounding proteins and cells via 2 classes of adhesion molecules, the integrins and IgCAMs. Integrins and IgCAMs propagate activation of multiple downstream signals that potentially impact cadherin adhesion. Here we discuss the known contributions of integrin and IgCAM signaling to the regulation of cadherin adhesion stability, endothelial barrier function, and vascular permeability. Emphasis is placed on known and prospective crosstalk signaling mechanisms between integrins, the IgCAMs- ICAM-1 and PECAM-1, and inter-endothelial cadherin adhesions, as potential strategic signaling nodes for multipartite regulation of cadherin adhesion.

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Section: Regulation Of Inter-endothelial Adherens Junctions Under Resmentioning

confidence: 99%

Control of vascular permeability by adhesion molecules

Sarelius

Glading²

2014

Tissue Barriers

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“…In epithelial tissues, the extracellular domain of cadherin forms adhesive contacts between neighboring cells, and its cytoplasmic domain binds β-catenin, which in turn binds the F-actin binding protein αE-catenin ( 5 ), the most widely expressed of the three α-catenin family members ( 6 ). αE-catenin binds strongly to the E-cadherin/β-catenin complex (K D ~1 nM) ( 7, 8 ), but more weakly to F-actin (K D ~1 μM) ( 9-11 ). Cell biological studies led to the hypothesis that αE-catenin directly links the E-cadherin/β-catenin complex to F-actin, consistent with its role in force transmission between cadherins and the actin cytoskeleton ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

“…The observed unbinding events were most likely caused by the dissociation of the intact cadherin-catenin complex from the suspended actin filament, rather than dissociation of αE-catenin from the E-cadherin/β-catenin heterodimer. In solution (without applied tension), the αE-catenin monomer binds strongly to E-cadherin/β-catenin (K D = 1 nM), but binds at least 1000x more weakly to F-actin ( 7-9, 13 ). At the concentrations in our experiments, any αE-catenin molecules that detached from the surface-bound cadherin-catenin complex would occupy a negligible number of binding sites on the actin filament ( 31 ).…”

Section: Introductionmentioning

confidence: 99%

The minimal cadherin-catenin complex binds to actin filaments under force

Buckley

Tan

Anderson

et al. 2014

Science

548

431

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Linkage between the adherens junction (AJ) and the actin cytoskeleton is required for tissue development and homeostasis. In vivo findings indicated that the AJ proteins E-cadherin, β-catenin, and the filamentous (F)-actin binding protein αE-catenin form a minimal cadherin-catenin complex that binds directly to F-actin. Biochemical studies challenged this model since the purified cadherin-catenin complex does not bind F-actin in solution. Here we reconciled this difference. Using an optical trap-based assay, we showed that the minimal cadherin-catenin complex formed stable bonds with an actin filament under force. Bond dissociation kinetics can be explained by a catch bond model in which force shifts the bond from a weakly to a strongly bound state. These results may explain how the cadherin-catenin complex transduces mechanical forces at cell-cell junctions.

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“…This value is less than the fivefold enrichment observed for integrins at focal contacts with fibronectin (19), suggesting that Ncad-Fc binding sites are partially saturated with Ncad-GFP molecules, leaving out an ∼55% population of diffusive N-cadherin. α-Catenin exhibited a very similar behavior to N-cadherin in both sptPALM and FRAP, suggesting that observed α-catenin is mostly in the monomeric form, which associates strongly with N-cadherin and β-catenin, and not in the dimeric form, which preferentially binds actin (20,21,34). Vinculin also exhibited a mixture of diffusion and confinement but did not associate with N-cadherin adhesions in this system.…”

Section: Discussionmentioning

confidence: 72%

Two-tiered coupling between flowing actin and immobilized N -cadherin/catenin complexes in neuronal growth cones

Garcia

Leduc

Lagardère

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Neuronal growth cones move forward by dynamically connecting actin-based motility to substrate adhesion, but the mechanisms at the individual molecular level remain unclear. We cultured primary neurons on N-cadherin-coated micropatterned substrates, and imaged adhesion and cytoskeletal proteins at the ventral surface of growth cones using single particle tracking combined to photoactivated localization microscopy (sptPALM). We demonstrate transient interactions in the second time scale between flowing actin filaments and immobilized N-cadherin/catenin complexes, translating into a local reduction of the actin retrograde flow. Normal actin flow on micropatterns was rescued by expression of a dominant negative N-cadherin construct competing for the coupling between actin and endogenous N-cadherin. Fluorescence recovery after photobleaching (FRAP) experiments confirmed the differential kinetics of actin and N-cadherin, and further revealed a 20% actin population confined at N-cadherin micropatterns, contributing to local actin accumulation. Computer simulations with relevant kinetic parameters modeled N-cadherin and actin turnover well, validating this mechanism. Such a combination of short-and long-lived interactions between the motile actin network and spatially restricted adhesive complexes represents a two-tiered clutch mechanism likely to sustain dynamic environment sensing and provide the force necessary for growth cone migration.growth cone | actin flow | N-cadherin adhesion | micropatterned substrates | single-molecule tracking G rowth cones are motile structures at the extremity of axons responsible for path finding and neurite extension during nervous system development and repair. Growth cones translate extracellular signals into directional migration through a coordinated regulation of cytoskeleton, adhesion, and membrane processes (1). At the cytoskeletal level, motility is generated by polarized actin treadmilling, which, together with myosin contraction, generates a continuous retrograde actin flow from the periphery to the base of growth cones (2-7). At the membrane level, adhesion proteins form dynamic bonds with immobilized extracellular ligands, allowing step-by-step locomotion (8).The molecular clutch model postulates that the mechanical coupling between ligand-bound transmembrane adhesion receptors and the actin flow allows traction forces to be transmitted to the substrate, resulting in local diminution of the retrograde flow and forward progression (9-11). Optical tweezers and flexible substrate experiments using microspheres coated with adhesion molecules revealed clutch-like mechanisms for integrins (12, 13), Ig cell adhesion molecules (14, 15), and cadherins (16,17). However, the mechanism of clutch engagement at the individual molecular level remains elusive. For integrin-based adhesion, single-molecule tracking experiments suggested that talin and vinculin could switch between a state bound to flowing actin and a state bound to immobilized integrins (18, 19). For cadherin-based adhesion,...

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Structural and Thermodynamic Characterization of Cadherin·β-Catenin·α-Catenin Complex Formation

Cited by 55 publications

References 48 publications

Control of vascular permeability by adhesion molecules

Control of vascular permeability by adhesion molecules

The minimal cadherin-catenin complex binds to actin filaments under force

Two-tiered coupling between flowing actin and immobilized N -cadherin/catenin complexes in neuronal growth cones

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