α-Catenin cytomechanics – role in cadherin-dependent adhesion and mechanotransduction

Barry, Adrienne K.; Tabdili, Hamid; Muhamed, Ismaeel; Wu, Jun; Shashikanth, Nitesh; Gómez, Guillermo A.; Yap, Alpha; Gottardi, Cara J.; Rooij, Johan de; Wang, Ning; Leckband, Deborah

doi:10.1242/dev.111419

Cited by 18 publications

(43 citation statements)

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“…The two-stage binding time course (Fig. 1C) was reported previously for several adhesion-competent classical cadherins (32,41,(47)(48)(49). Extracellular domain deletions and binding site mutations mapped the fast, initial rise in binding probability P1 to trans-dimerization between N-terminal EC1 domains (41,49).…”

Section: Activating But Not Neutral Antibody Increases Cadherin Transsupporting

confidence: 77%

“…The strengthening of cadherin-mediated intercellular adhesion has been attributed to several mechanisms, including GTPase activity (27)(28)(29)(30)(31), enhanced cadherin-cytoskeletal interactions (5,(32)(33)(34)(35), cadherin catch bonds (36), cadherin clustering (19,37,38), and altered cortical tension (5,6). Demonstrating that Colo 205 aggregation was caused by the allosteric regulation of E-cadherin required a demonstration that specific perturbations, which do not affect the binding site directly, caused quantitative changes in the E-cadherin affinity.…”

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confidence: 99%

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Allosteric Regulation of E-Cadherin Adhesion

Shashikanth¹,

Petrova

Park³

et al. 2015

Journal of Biological Chemistry

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Background: Measured binding kinetics between Colo 205 cells tested the postulate that E-cadherin adhesion is allosterically regulated. Results: p120 catenin dephosphorylation or cell treatment with activating anti-E-cadherin antibody increased E-cadherin binding affinities by 2-3-fold. Conclusion: Perturbations that do not directly affect the binding site enhanced the adhesive function of E-cadherin. Significance: These biophysical measurements demonstrated that E-cadherin is allosterically regulated.

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Section: Activating But Not Neutral Antibody Increases Cadherin Transsupporting

confidence: 77%

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confidence: 99%

Allosteric Regulation of E-Cadherin Adhesion

Shashikanth¹,

Petrova

Park³

et al. 2015

Journal of Biological Chemistry

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“…In addition to signaling through β-catenin, several recent studies have characterized a force-dependent interaction between vinculin and α-catenin, another protein linking AJs to the cytoskeleton (Huveneers et al, 2012;le Duc et al, 2010;Yao et al, 2014;Yonemura et al, 2010). Vinculin is recruited to AJs in a forcedependent manner by α-catenin, which results in strengthening of the adhesion and increased cell contractility (Barry et al, 2014;Yao et al, 2014). This result indicates that integrins and cadherins might share a common mechano-sensitive mechanism, in which vinculininduced stabilization of either FAs or AJs affects downstream signaling pathways.…”

Section: Cadherins Sense Intercellular Forcesmentioning

confidence: 99%

Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease

Schroer

Merryman

2015

Journal of Cell Science

117

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Fibrotic cardiac disease, a leading cause of death worldwide, manifests as substantial loss of function following maladaptive tissue remodeling. Fibrosis can affect both the heart valves and the myocardium and is characterized by the activation of fibroblasts and accumulation of extracellular matrix. Valvular interstitial cells and cardiac fibroblasts, the cell types responsible for maintenance of cardiac extracellular matrix, are sensitive to changing mechanical environments, and their ability to sense and respond to mechanical forces determines both normal development and the progression of disease. Recent studies have uncovered specific adhesion proteins and mechano-sensitive signaling pathways that contribute to the progression of fibrosis. Integrins form adhesions with the extracellular matrix, and respond to changes in substrate stiffness and extracellular matrix composition. Cadherins mechanically link neighboring cells and are likely to contribute to fibrotic disease propagation. Finally, transition to the active myofibroblast phenotype leads to maladaptive tissue remodeling and enhanced mechanotransductive signaling, forming a positive feedback loop that contributes to heart failure. This Commentary summarizes recent findings on the role of mechanotransduction through integrins and cadherins to perpetuate mechanically induced differentiation and fibrosis in the context of cardiac disease.

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“…Intercellular adhesive complexes not only regulate cell-to-cell cohesion and tissue barrier integrity, but also transduce force to instruct cell functions, alter cell shape and regulate tissue organization (Desai et al, 2013;Ladoux et al, 2010;le Duc et al, 2010;Leckband and de Rooij, 2014;Lecuit et al, 2011;Liu et al, 2010;Tepass et al, 2002;Tzima et al, 2005;Yonemura et al, 2010). Fluctuations in tension also trigger junction remodeling in endothelia and in epithelia, and these changes contribute to the mechanical reinforcement of adhesions (Barry et al, 2014(Barry et al, , 2015Liu et al, 2010;Thomas et al, 2013;Yonemura et al, 2010). Studies increasingly reveal how mechanotransduction at cell-to-cell adhesions in vivo impacts upon physiology in different mechanical contexts, such as at interendothelial junctions near regions of disturbed flow and during morphogenesis (Hahn and Schwartz, 2009;Schluck et al, 2013;Weber et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…The rudiments of intercellular mechanotransduction mechanisms have been identified in only a few cases (Barry et al, 2014;Collins et al, 2012;Kim et al, 2015;le Duc et al, 2010;Tzima et al, 2005;Yonemura et al, 2010). E-cadherin complexes at epithelial intercellular junctions are force sensitive (Barry et al, 2014;le Duc et al, 2010;Thomas et al, 2013;Yonemura et al, 2010), and α-catenin is an identified force-transducing protein in these complexes (Yonemura et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

E-cadherin-mediated force transduction signals regulate global cell mechanics

Muhamed

Sehgal

et al. 2016

Journal of Cell Science

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104

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This report elucidates an E-cadherin-based force-transduction pathway that triggers changes in cell mechanics through a mechanism requiring epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), and the downstream formation of new integrin adhesions. This mechanism operates in addition to local cytoskeletal remodeling triggered by conformational changes in the E-cadherin-associated protein α-catenin, at sites of mechanical perturbation. Studies using magnetic twisting cytometry (MTC), together with traction force microscopy (TFM) and confocal imaging identified force-activated E-cadherin-specific signals that integrate cadherin force transduction, integrin activation and cell contractility. EGFR is required for the downstream activation of PI3K and myosin-II-dependent cell stiffening. Our findings also demonstrated that α-catenin-dependent cytoskeletal remodeling at perturbed E-cadherin adhesions does not require cell stiffening. These results broaden the repertoire of E-cadherin-based force transduction mechanisms, and define the force-sensitive signaling network underlying the mechano-chemical integration of spatially segregated adhesion receptors.

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α-Catenin cytomechanics – role in cadherin-dependent adhesion and mechanotransduction

Cited by 18 publications

References 1 publication

Allosteric Regulation of E-Cadherin Adhesion

Allosteric Regulation of E-Cadherin Adhesion

Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease

E-cadherin-mediated force transduction signals regulate global cell mechanics

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