The formation of ordered nanoclusters controls cadherin anchoring to actin and cell–cell contact fluidity

Strale, Pierre‐Olivier; Duchesne, Laurence; Peyret, Grégoire; Montel, Lorraine; Nguyen, Thao; Png, Evelyn; Tampé, Robert; Troyanovsky, Sergey M.; Hénon, Sylvie; Ladoux, Benoît; Mège, René-Marc

doi:10.1083/jcb.201410111

Cited by 78 publications

(68 citation statements)

References 57 publications

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“…F-actin at the Ecad:Fc MTM properly assembled into an apical ring, and F-actin levels at junctions at the Ecad:Fc MTM reached 66% (±25%, n = 40) of levels within native junctions. This finding is consistent with previous data indicating that highly mobile fractions of E-cadherin can disrupt cytoskeletal attachment by reducing E-cadherin cluster formation (32). Additionally, the rigid, inactive nature of the MTM creates a different mechanical boundary condition than occurs at a native cell-cell junction, again likely affecting cytoskeletal organization and perhaps accounting for the increase in 2D hybrid junction length observed with high density cells.…”

Section: Resultssupporting

confidence: 82%

“…The immobility of Ecad:Fc is likely responsible for the elevated mobile fraction and slight reduction in the level of cellular E-cadherin at the Ecad:Fc MTM. An increased mobile fraction has been attributed to a reduction in the formation of cadherin nanoclusters (32), and data from studies using 2D-supported membranes functionalized with E-cadherin extracellular domain demonstrated that some degree of E-cadherin mobility is essential to allow clusters to nucleate and stabilize (19).…”

Section: Resultsmentioning

confidence: 99%

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Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction

Cohen

Gloerich

Nelson

2016

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

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Epithelial monolayers undergo self-healing when wounded. During healing, cells collectively migrate into the wound site, and the converging tissue fronts collide and form a stable interface. To heal, migrating tissues must form cell-cell adhesions and reorganize from the front-rear polarity characteristic of cell migration to the apicalbasal polarity of an epithelium. However, identifying the "stop signal" that induces colliding tissues to cease migrating and heal remains an open question. Epithelial cells form integrin-based adhesions to the basal extracellular matrix (ECM) and E-cadherinmediated cell-cell adhesions on the orthogonal, lateral surfaces between cells. Current biological tools have been unable to probe this multicellular 3D interface to determine the stop signal. We addressed this problem by developing a unique biointerface that mimicked the 3D organization of epithelial cell adhesions. This "minimal tissue mimic" (MTM) comprised a basal ECM substrate and a vertical surface coated with purified extracellular domain of E-cadherin, and was designed for collision with the healing edge of an epithelial monolayer. Three-dimensional imaging showed that adhesions formed between cells, and the E-cadherin-coated MTM resembled the morphology and dynamics of native epithelial cell-cell junctions and induced the same polarity transition that occurs during epithelial self-healing. These results indicate that E-cadherin presented in the proper 3D context constitutes a minimum essential stop signal to induce self-healing. That the Ecad:Fc MTM stably integrated into an epithelial tissue and reduced migration at the interface suggests that this biointerface is a complimentary approach to existing tissue-material interfaces.cadherin | wound healing | biomaterial | biomimetic | collective migration

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction

Cohen

Gloerich

Nelson

2016

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

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“…Studies with E-cadherin (E-cad)-coated substrates have revealed the existence of E-cad nanoclusters as fundamental units for cell-cell adhesion, and their existence has been confirmed by super-resolution imaging of mammalian cellcell contacts (Wu et al, 2015;Strale et al, 2015), as well as in Drosophila (Truong Quang et al, 2013). In addition, both E-and N-cad-coated deformable pillars allow the measurement of the traction forces that are exerted by a single cell across cadherin bonds.…”

Section: Ecm Sensingmentioning

confidence: 99%

How cells respond to environmental cues – insights from bio-functionalized substrates

Ruprecht

Monzo

Ravasio

et al. 2016

Journal of Cell Science

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Biomimetic materials have long been the (he)art of bioengineering. They usually aim at mimicking in vivo conditions to allow in vitro culture, differentiation and expansion of cells. The past decade has witnessed a considerable amount of progress in soft lithography, bioinspired micro-fabrication and biochemistry, allowing the design of sophisticated and physiologically relevant micro-and nanoenvironments. These systems now provide an exquisite toolbox with which we can control a large set of physicochemical environmental parameters that determine cell behavior. Biofunctionalized surfaces have evolved from simple protein-coated solid surfaces or cellular extracts into nano-textured 3D surfaces with controlled rheological and topographical properties. The mechanobiological molecular processes by which cells interact and sense their environment can now be unambiguously understood down to the single-molecule level. This Commentary highlights recent successful examples where bio-functionalized substrates have contributed in raising and answering new questions in the area of extracellular matrix sensing by cells, cell-cell adhesion and cell migration. The use, the availability, the impact and the challenges of such approaches in the field of biology are discussed.

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“…Mutations here cause measurable changes in mechanical coupling to the actin cytoskeleton but do not affect cell-cell adhesion (65). The same region of ECad is important for a proposed conformational change involved in inside-out activation (66,67).…”

Section: Discussionmentioning

confidence: 80%

Fbxo45 binds SPRY motifs in the extracellular domain of N-cadherin and regulates neuron migration during brain development

Jiménez

Kon

et al. 2019

Preprint

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ABSTRACTSeveral events during normal development of the mammalian neocortex depend on N-cadherin, including the radial migration of immature projection neurons into the cortical plate. Remarkably, radial migration requires the N-cadherin extracellular domain but not N-cadherin-dependent homophilic cell-cell adhesion, suggesting that other N-cadherin-binding proteins may be involved. We used proximity ligation and affinity purification proteomics to identify N-cadherin-binding proteins. Both screens detected MycBP2 and SPRY-domain protein Fbxo45, two components of an intracellular E3 ubiquitin ligase. Fbxo45 appears to be secreted by a non-classical mechanism, not involving a signal peptide and not requiring endoplasmic reticulum to Golgi transport. Fbxo45 binding requires N-cadherin SPRY motifs that are not involved in cell-cell adhesion. SPRY-mutant N-cadherin does not support radial migration in vivo. Radial migration was similarly inhibited when Fbxo45 expression was suppressed. The results suggest that projection neuron migration requires both Fbxo45 and binding of Fbxo45 or another protein to SPRY motifs in the extracellular domain of N-cadherin.

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The formation of ordered nanoclusters controls cadherin anchoring to actin and cell–cell contact fluidity

Abstract: Visualization of single cadherins within cell membrane at nanometric resolution shows that E-cadherins arrange in ordered clusters and that these clusters control the anchoring of cadherin to actin and cell–cell contact fluidity.

Cited by 78 publications

References 57 publications

Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction

Epithelial self-healing is recapitulated by a 3D biomimetic E-cadherin junction

How cells respond to environmental cues – insights from bio-functionalized substrates

Fbxo45 binds SPRY motifs in the extracellular domain of N-cadherin and regulates neuron migration during brain development

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