scholarly journals Lateral Dimerization of the E-cadherin Extracellular Domain Is Necessary but Not Sufficient for Adhesive Activity

2002 ◽  
Vol 277 (22) ◽  
pp. 19600-19608 ◽  
Author(s):  
Masayuki Ozawa
Keyword(s):  
Extracellular Domain ◽  
E Cadherin

Contributions of extracellular and intracellular domains of full length and chimeric cadherin molecules to junction assembly in epithelial cells

1998 ◽  
Vol 111 (9) ◽  
pp. 1305-1318 ◽  
Author(s):  
S.M. Norvell ◽  
K.J. Green
Keyword(s):  
Epithelial Cells ◽  
Cell Surface ◽  
Extracellular Domain ◽  
Full Length ◽  
Intracellular Domain ◽  
Epithelial Junctions ◽  
Intracellular Domains ◽  
E Cadherin ◽  
Cell Cell

The integrity of cell-cell junctions in epithelial cells depends on functional interactions of both extracellular and intracellular domains of cadherins with other junction proteins. To examine the roles of the different domains of E-cadherin and desmoglein in epithelial junctions, we stably expressed full length desmoglein 1 and chimeras of E-cadherin and desmoglein 1 in A431 epithelial cells. Full length desmoglein 1 was able to incorporate into or disrupt endogenous desmosomes depending on expression level. Each of the chimeric cadherin molecules exhibited distinct localization patterns at the cell surface. A chimera of the desmoglein 1 extracellular domain and the E-cadherin intracellular domain was distributed diffusely at the cell surface while the reverse chimera, comprising the E-cadherin extracellular domain and the desmoglein 1 intracellular domain, localized in large, sometimes contiguous patches at cell-cell interfaces. Nevertheless, both constructs disrupted desmosome assembly. Expression of constructs containing the desmoglein 1 cytoplasmic domain resulted in approximately a 3-fold decrease in E-cadherin bound to plakoglobin and a 5- to 10-fold reduction in the steady-state levels of the endogenous desmosomal cadherins, desmoglein 2 and desmocollin 2, possibly contributing to the dominant negative effect of the desmoglein 1 tail. In addition, biochemical analysis of protein complexes in the stable lines revealed novel in vivo protein interactions. Complexes containing beta-catenin and desmoglein 1 were identified in cells expressing constructs containing the desmoglein 1 tail. Furthermore, interactions were identified between endogenous E-cadherin and the chimera containing the E-cadherin extracellular domain and the desmoglein 1 intracellular domain providing in vivo evidence for previously predicted lateral interactions of E-cadherin extracellular domains.

scholarly journals Conformational changes of the recombinant extracellular domain of E-cadherin upon calcium binding

1994 ◽  
Vol 223 (3) ◽  
pp. 1019-1026 ◽  
Author(s):  
Sabine POKUTTA ◽  
Kurt HERRENKNECHT ◽  
Rolf KEMLER ◽  
Jurgen ENGEL
Keyword(s):  
Conformational Changes ◽  
Calcium Binding ◽  
Extracellular Domain ◽  
E Cadherin

scholarly journals Direct visualization of the extracellular binding structure of E-cadherins in liquid

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Teiko Shibata-Seki ◽  
Masato Nagaoka ◽  
Mitsuaki Goto ◽  
Eiry Kobatake ◽  
Toshihiro Akaike
Keyword(s):  
Chimeric Protein ◽  
Chelating Agent ◽  
Extracellular Domain ◽  
Cell Morphogenesis ◽  
X Ray ◽  
Dependent Cell ◽  
And Function ◽  
Direct Confirmation ◽  
Good Agreement ◽  
E Cadherin

Abstract E-cadherin is a key Ca-dependent cell adhesion molecule, which is expressed on many cell surfaces and involved in cell morphogenesis, embryonic development, EMT, etc. The fusion protein E-cad-Fc consists of the extracellular domain of E-cadherin and the IgG Fc domain. On plates coated with this chimeric protein, ES/iPS cells are cultivated particularly well and induced to differentiate. The cells adhere to the plate via E-cad-Fc in the presence of Ca2+ and detach by a chelating agent. For the purpose of clarifying the structures of E-cad-Fc in the presence and absence of Ca2+, we analyzed the molecular structure of E-cad-Fc by AFM in liquid. Our AFM observations revealed a rod-like structure of the entire extracellular domain of E-cad-Fc in the presence of Ca2+ as well as trans-binding of E-cad-Fc with adjacent molecules, which may be the first, direct confirmation of trans-dimerization of E-cadherin. The observed structures were in good agreement with an X-ray crystallographic model. Furthermore, we succeeded in visualizing the changes in the rod-like structure of the EC domains with and without calcium. The biomatrix surface plays an important role in cell culture, so the analysis of its structure and function may help promote cell engineering based on cell recognition.

The extracellular domain of E cadherin linked to invasiveness in colorectal cancer: a new resistance and relapses monitoring serum-bio marker?

2017 ◽  
Vol 143 (7) ◽  
pp. 1177-1190 ◽  
Author(s):  
Niki Christou ◽  
Aurélie Perraud ◽  
Sabrina Blondy ◽  
Marie-Odile Jauberteau ◽  
Serge Battu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Extracellular Domain ◽  
E Cadherin

scholarly journals Transmembrane control of cadherin-mediated cell adhesion: a 94 kDa protein functionally associated with a specific region of the cytoplasmic domain of E-cadherin.

1989 ◽  
Vol 1 (1) ◽  
pp. 37-44 ◽  
Author(s):  
A Nagafuchi ◽  
M Takeichi
Keyword(s):  
Cell Adhesion ◽  
Extracellular Domain ◽  
Cytoplasmic Domain ◽  
Cytoplasmic Domains ◽  
Mutant Proteins ◽  
L Cells ◽  
Binding Function ◽  
Mutant Polypeptides ◽  
E Cadherin ◽  
Cell Cell

Cadherins are a family of transmembrane glycoproteins which play a key role in Ca(2+)-dependent cell-cell adhesion. Cytoplasmic domains of these molecules are anchored to the cell cytoskeleton and are required for cadherin function. To elucidate how the function of cadherins is controlled through their cytoplasmic domains, we deleted five different regions in the cytoplasmic domain of E-cadherin. After transfecting L cells with cDNA encoding the mutant polypeptides, we assayed aggregating activity of these transfectants; all these mutant proteins were shown to have an extracellular domain with normal Ca(2+)-sensitivity and molecular weight. Two mutant polypeptides with deletions in the carboxy half of the cytoplasmic domain, however, did not promote cell-cell adhesion and had also lost the ability to bind to the cytoskeleton, whereas the mutant molecules with deletions of other regions retained the ability to promote cell adhesion and to anchor to the cytoskeleton. Thus, the cytoplasmic domain contains a subdomain which was involved in the cell adhesion and cytoskeleton-binding functions. When E-cadherin in F9 cells or in L cells transfected with wild-type or functional mutant cadherin polypeptides was solubilized with nonionic detergents and immunoprecipitated, two additional 94 and 102 kDa components were coprecipitated. The 94 kDa component, however, was not detected in the immunoprecipitates from cells expressing the mutant cadherins which had lost the adhesive function. These results suggest that the interaction of the carboxy half of the cytoplasmic domain with the 94 kDa component regulates the cell binding function of the extracellular domain of E-cadherin.

scholarly journals Adhesive But Not Lateral E-cadherin Complexes Require Calcium and Catenins for Their Formation

1998 ◽  
Vol 142 (3) ◽  
pp. 837-846 ◽  
Author(s):  
Nikolai A. Chitaev ◽  
Sergey M. Troyanovsky
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitution ◽  
Calcium Ions ◽  
Extracellular Domain ◽  
Extracellular Calcium ◽  
The Third ◽  
Complex Process ◽  
Double Amino Acid ◽  
Parallel Fashion ◽  
E Cadherin

We examined intercadherin interactions in epithelial A-431 cells producing endogenous E-cadherin and recombinant forms of E-cadherin tagged either by myc or by flag epitopes. Three distinct E-cadherin complexes were found. The first is a conventional E-cadherin–catenin complex consisting of one E-cadherin molecule linked either to β-catenin/α-catenin or to plakoglobin/α-catenin dimers. The second is a lateral E-cadherin complex incorporating two E-cadherin– catenin conventional complexes combined in parallel fashion via dimerization of the NH2-terminal extracellular domain of E-cadherin. The third complex is likely to contain two E-cadherin–catenin conventional complexes derived from two opposing cells and arranged in an antiparallel fashion. Formation of the antiparallel but not lateral complex strictly depends on extracellular calcium and E-cadherin binding to catenins. Double amino acid substitution Trp156Ala/Val157Gly within the extracellular NH2-terminal E-cadherin domain completely abolished both lateral and antiparallel inter–E-cadherin association. These data support an idea that the antiparallel complex has the adhesion function. Furthermore, they allow us to suggest that antiparallel complexes derive from lateral dimers and this complex process requires catenins and calcium ions.

The soluble extracellular domain of E‐cadherin interferes with EPEC adherenceviainteraction with the Tir:intimin complex

2018 ◽  
Vol 32 (12) ◽  
pp. 6860-6868
Author(s):  
Frédéric H. Login ◽  
Helene H. Jensen ◽  
Gitte A. Pedersen ◽  
Manuel R. Amieva ◽  
Lene N. Nejsum
Keyword(s):  
Extracellular Domain ◽  
E Cadherin

scholarly journals Rhomboid-Like-2 Intramembrane Protease Mediates Metalloprotease-Independent Regulation of Cadherins

2019 ◽  
Vol 20 (23) ◽  
pp. 5958
Author(s):  
Chiara Battistini ◽  
Michael Rehman ◽  
Marco Avolio ◽  
Alessia Arduin ◽  
Donatella Valdembri ◽  
...  
Keyword(s):  
Translational Regulation ◽  
Functional Role ◽  
Extracellular Domain ◽  
Negative Regulators ◽  
Similar Activity ◽  
Cell Adhesive ◽  
Functional Pathway ◽  
Processing Mechanism ◽  
E Cadherin

Cadherins are a major family of cell–cell adhesive receptors, which are implicated in development, tissue homeostasis, and cancer. Here, we show a novel mechanism of post-translational regulation of E-cadherin in cancer cells by an intramembrane protease of the Rhomboid family, RHBDL2, which leads to the shedding of E-cadherin extracellular domain. In addition, our data indicate that RHBDL2 mediates a similar activity on VE-cadherin, which is selectively expressed by endothelial cells. We show that RHBDL2 promotes cell migration, which is consistent with its ability to interfere with the functional role of cadherins as negative regulators of motility; moreover, the two players appear to lie in the same functional pathway. Importantly, we show that RHBDL2 expression is induced by the inflammatory chemokine TNFα. The E-cadherin extracellular domain is known to be released by metalloproteases (MMPs); however, here, we provide evidence of a novel MMP-independent, TNFα inducible, E-cadherin processing mechanism that is mediated by RHBDL2. Thus, the intramembrane protease RHBDL2 is a novel regulator of cadherins promoting cell motility.

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