Giving the right tug for migration: Cadherins in tissue movements

Becker, Sarah F. S.; Langhe, Rahul; Huang, Chaolie; Wedlich, Doris; Kashef, Jubin

doi:10.1016/j.abb.2012.02.013

Cited by 20 publications

(13 citation statements)

References 229 publications

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“…A decrease or increase of cadherin-11 protein levels caused by translation blocking morpholino oligonucleotides (MO), or overexpression leads to defects in migration (Borchers et al, 2001; Kashef et al, 2009). Cadherin-11 is a type II classical cadherin that contains five extracellular repeats (EC1-5) with immunoglobulin-like folds separated by flexible linkers, followed by a transmembrane and cytoplasmic domain (Becker et al, 2012). The membrane-distal EC1 possesses highly conserved tryptophans and the QAV motif, which function as the adhesive site for homophilic binding of cadherins on neighboring cells (Boggon et al, 2002; Patel et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

Abbruzzese

Becker

Kashef

et al. 2016

Developmental Biology

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The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell–cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo.

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Section: Introductionmentioning

confidence: 99%

ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

Abbruzzese

Becker

Kashef

et al. 2016

Developmental Biology

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“…Conversely, loss of the E-cadherin function correlates with tumorigenesis [4], embryonic lethality [5], [6] and loss of pluripotency of embryonic stem cells [7]. To foster firm adhesion the cytoplasmic part of E-cadherin must be linked to the actin cytoskeleton via β- and α-catenin and additionally, these cadherin-catenin complexes become clustered in adherens junctions [8]. Cadherin adhesion has also been reported to participate in mechanosensing by binding to plakoglobin and recruiting keratin filaments to sites of tension at the cell membrane [9].…”

Section: Introductionmentioning

confidence: 99%

Covalent and Density-Controlled Surface Immobilization of E-Cadherin for Adhesion Force Spectroscopy

et al. 2014

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E-cadherin is a key cell-cell adhesion molecule but the impact of receptor density and the precise contribution of individual cadherin ectodomains in promoting cell adhesion are only incompletely understood. Investigating these mechanisms would benefit from artificial adhesion substrates carrying different cadherin ectodomains at defined surface density. We therefore developed a quantitative E-cadherin surface immobilization protocol based on the SNAP-tag technique. Extracellular (EC) fragments of E-cadherin fused to the SNAP-tag were covalently bound to self-assembled monolayers (SAM) of thiols carrying benzylguanine (BG) head groups. The adhesive functionality of the different E-cadherin surfaces was then assessed using cell spreading assays and single-cell (SCSF) and single-molecule (SMSF) force spectroscopy. We demonstrate that an E-cadherin construct containing only the first and second outmost EC domain (E1-2) is not sufficient for mediating cell adhesion and yields only low single cadherin-cadherin adhesion forces. In contrast, a construct containing all five EC domains (E1-5) efficiently promotes cell spreading and generates strong single cadherin and cell adhesion forces. By varying the concentration of BG head groups within the SAM we determined a lateral distance of 5–11 nm for optimal E-cadherin functionality. Integrating the results from SCMS and SMSF experiments furthermore demonstrated that the dissolution of E-cadherin adhesion contacts involves a sequential unbinding of individual cadherin receptors rather than the sudden rupture of larger cadherin receptor clusters. Our method of covalent, oriented and density-controlled E-cadherin immobilization thus provides a novel and versatile platform to study molecular mechanisms underlying cadherin-mediated cell adhesion under defined experimental conditions.

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“…For the recognition of cell-cell contact in CIL adhesion molecules such as cadherins were proposed [15,16]. Among them, N-Cadherin is expressed during CNC cell migration and promotes CNC migration in vivo .…”

Section: Introductionmentioning

confidence: 99%

Cadherin-11 Mediates Contact Inhibition of Locomotion during Xenopus Neural Crest Cell Migration

2013

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Collective cell migration is an essential feature both in embryonic development and cancer progression. The molecular mechanisms of these coordinated directional cell movements still need to be elucidated. The migration of cranial neural crest (CNC) cells during embryogenesis is an excellent model for collective cell migration in vivo. These highly motile and multipotent cells migrate directionally on defined routes throughout the embryo. Interestingly, local cell-cell interactions seem to be the key force for directionality. CNC cells can change their migration direction by a repulsive cell response called contact inhibition of locomotion (CIL). Cell protrusions collapse upon homotypic cell-cell contact and internal repolarization leads to formation of new protrusions toward cell-free regions. Wnt/PCP signaling was shown to mediate activation of small RhoGTPase RhoA and inhibition of cell protrusions at the contact side. However, the mechanism how a cell recognizes the contact is poorly understood. Here, we demonstrate that Xenopus cadherin-11 (Xcad-11) mediated cell-cell adhesion is necessary in CIL for directional and collective migration of CNC cells. Reduction of Xcad-11 adhesive function resulted in higher invasiveness of CNC due to loss of CIL. Additionally, transplantation analyses revealed that CNC migratory behaviour in vivo is non-directional and incomplete when Xcad-11 adhesive function is impaired. Blocking Wnt/PCP signaling led to similar results underlining the importance of Xcad-11 in the mechanism of CIL and directional migration of CNC.

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Giving the right tug for migration: Cadherins in tissue movements

Cited by 20 publications

References 229 publications

ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

Covalent and Density-Controlled Surface Immobilization of E-Cadherin for Adhesion Force Spectroscopy

Cadherin-11 Mediates Contact Inhibition of Locomotion during Xenopus Neural Crest Cell Migration

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