Force-induced changes of α-catenin conformation stabilize vascular junctions independently of vinculin

Duong, Cao Nguyen; Brückner, Randy; Schmitt, Martina; Nottebaum, Astrid F.; Braun, Laura J.; Brickwedde, Marika Meyer Zu; Ipe, Ute; Bruch, Hermann vom; Schöler, Hans R.; Trapani, Giuseppe; Trappmann, Britta; Ebrahimkutty, Mirsana; Huveneers, Stephan; Rooij, Johan de; Ishiyama, Noboru; Ikura, Mitsuhiko; Vestweber, Dietmar

doi:10.1242/jcs.259012

Cited by 14 publications

(13 citation statements)

References 42 publications

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“…The interaction of the VE-Cadherin -Catenin complex with the actin cytoskeleton stabilizes the AJs and maintains endothelial monolayer integrity (19)(20)(21). Tension on the VE-Cadherin complex results in unfolding of α-Catenin, which enhances its Actinbinding affinity and exposes a cryptic binding site for Vinculin (22)(23)(24)(25)(26)(27)(28). The Vinculin -α-Catenin interaction drives α-Catenin-mediated mechanotransduction and preserves junctional integrity during force-dependent remodelling in cultured endothelial and epithelial cells (22,25,(29)(30)(31)(32).…”

Section: Introductionmentioning

confidence: 99%

“…Tension on the VE–cadherin complex results in unfolding of α-catenin, which enhances its actin-binding affinity and exposes a cryptic binding site for vinculin ( 16 , 22 , 23 , 24 , 25 , 26 , 27 ). The vinculin–α-catenin interaction drives α-catenin-mediated mechanotransduction and preserves junctional integrity during force-dependent remodelling in cultured endothelial and epithelial cells ( 22 , 25 , 28 , 29 , 30 , 31 ).…”

Section: Introductionmentioning

confidence: 99%

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Vinculin strengthens the endothelial barrier during vascular development

et al. 2022

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Remodelling of cell-cell junctions is crucial for proper tissue development and barrier function. The Cadherin-based adherens junctions anchor via β-Catenin and α-Catenin to the actomyosin cytoskeleton, together forming a junctional mechanotransduction complex. Tension-induced conformational changes in the mechanosensitive α-Catenin protein induce junctional Vinculin recruitment. In endothelial cells, Vinculin protects the remodelling VE-Cadherin junctions. In this study, we have addressed the role of Vinculin in endothelial barrier function in the developing vasculature. In vitro experiments, using endothelial cells in which α-Catenin was replaced by a Vinculin-binding deficient mutant, showed that junctional recruitment of Vinculin promotes endothelial barrier function. To assess the role of Vinculin within blood vessels in vivo, we next investigated barrier function in the vasculature of Vinculin knockout zebrafish. In the absence of Vinculin, sprouting angiogenesis and vessel perfusion still occurred. Intriguingly, the absence of Vinculin made the blood vessels more permeable for 10 kDa dextran molecules, but not for larger tracers. Taken together, our findings demonstrate that Vinculin strengthens the endothelial barrier and prevents vascular leakage in developing vessels.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Vinculin strengthens the endothelial barrier during vascular development

et al. 2022

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“…We employed a Vinculin biosensor to assay the force distribution next to the contracting cells ( Kong et al, 2019 ) and obtained an estimation for the reach of the pulling force by the contracting cell. This biosensor is based on the force-dependent conformational change of alpha-Catenin (alpha-Cat), a component of adherence junctions and binding partner of E-Cad ( Choi et al, 2012 ; Rangarajan and Izard, 2012 ; Yao et al, 2014 ; Duong et al, 2021 ). In the closed state, the central mechanosensitive modulatory (M) domain of alpha-Cat is inaccessible to the D1 domain of Vinculin.…”

Section: Resultsmentioning

confidence: 99%

The Lateral Epidermis Actively Counteracts Pulling by the Amnioserosa During Dorsal Closure

Zhang

et al. 2022

Front. Cell Dev. Biol.

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Dorsal closure is a prominent morphogenetic process during Drosophila embryogenesis, which involves two epithelial tissues, that is, the squamous amnioserosa and the columnar lateral epidermis. Non-muscle myosin II-driven constriction in the amnioserosa leads to a decrease in the apical surface area and pulls on the adjacent lateral epidermis, which subsequently moves dorsally. The pull by the amnioserosa becomes obvious in an elongation of the epidermal cells, especially of those in the first row. The contribution of the epidermal cell elongation has remained unclear to dorsal closure. Cell elongation may be a mere passive consequence or an active response to the pulling by the amnioserosa. Here, we found that the lateral epidermis actively responds. We analyzed tensions within tissues and cell junctions by laser ablation before and during dorsal closure, the elliptical and dorsal closure stages, respectively. Furthermore, we genetically and optochemically induced chronic and acute cell contraction, respectively. In this way, we found that tension in the epidermis increased during dorsal closure. A correspondingly increased tension was not observed at individual junctions, however. Junctional tension even decreased during dorsal closure in the epidermis. We strikingly observed a strong increase of the microtubule amount in the epidermis, while non-muscle myosin II increased in both tissues. Our data suggest that the epidermis actively antagonizes the pull from the amnioserosa during dorsal closure and the increased microtubules might help the epidermis bear part of the mechanical force.

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“…To test this, we probed for tension-sensitive changes in the conformation of α-catenin at head-on versus side-side contacts. Mechanical tension opens the central M-domain of α-catenin 25 and also unfolds the autoinhibited alpha1 helix in the F-actin-binding site (ABD) 22 ; these conformational changes are detectable with the α18 monoclonal 25 and VD7 polyclonal antibodies 26 , respectively (Fig 4E). Consistently, we found that staining for both α18 and VD7, corrected for total α-catenin, was more intense in AJ at head-on contacts compared with side-to-side contacts (Fig 4F, G).…”

Section: Resultsmentioning

confidence: 99%

“…Rat monoclonal antibody against α-catenin M-domain (α18) was kindly provided by Dr. A. Nagafuchi (Kumamoto University, Japan). Rabbit polyclonal antibody against a-catenin ABD (VD7) has been described before 26 .…”

Section: Star Methodsmentioning

confidence: 99%

An E-cadherin-actin clutch translates the mechanical force of cortical flow for cell-cell contact to inhibit epithelial cell locomotion

Noordstra

Hermoso

Schimmel

et al. 2021

Preprint

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Adherens junctions (AJs) fundamentally mediate cell-cell adhesion, yet the mechanisms that determine where or when AJs assemble are not understood. Here we reveal a mechanosensitive clutch that initiates AJ assembly. Before cell-cell contact, alpha-catenin couples surface E-cadherin complexes to retrograde flow of the actin cortex. Cortical flows with opposed orientations persist after contact, applying tension to alpha-catenin within trans-ligated cadherin complexes. Tension unfolds the alpha-catenin actin-binding domain (ABD), which is expected to mediate a catch bond with F-actin. However, catch bond behaviour is not sufficient for AJ assembly in a molecular clutch model. Instead, it is also necessary for the activated ABD to promote cis-clustering of E-cadherin molecules by bundling F-actin. Thus, this alpha-catenin clutch transduces the mechanical signal of cortical flow to assemble AJs.

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Force-induced changes of α-catenin conformation stabilize vascular junctions independently of vinculin

Cited by 14 publications

References 42 publications

Vinculin strengthens the endothelial barrier during vascular development

Vinculin strengthens the endothelial barrier during vascular development

The Lateral Epidermis Actively Counteracts Pulling by the Amnioserosa During Dorsal Closure

An E-cadherin-actin clutch translates the mechanical force of cortical flow for cell-cell contact to inhibit epithelial cell locomotion

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