Adherens Junctions in Myelinating Schwann Cells Stabilize Schmidt-Lanterman Incisures via Recruitment of p120 Catenin to E-Cadherin

E-Cadherin is a Ca2+-dependent cell-cell adhesion molecule at adherens junctions (AJs) of epithelial cells. A fragment of N-cadherin lacking its extracellular region serves as a dominant negative mutant (DN) and inhibits cell-cell adhesion activity of E-cadherin, but its mode of action remains to be elucidated. Nectin is a Ca2+-independent immunoglobulin-like cell-cell adhesion molecule at AJs and is associated with E-cadherin through their respective peripheral membrane proteins, afadin and catenins, which connect nectin and cadherin to the actin cytoskeleton, respectively. We showed here that overexpression of nectin capable of binding afadin, but not a mutant incapable of binding afadin, reduced the inhibitory effect of N-cadherin DN on the cell-cell adhesion activity of E-cadherin in keratinocytes. Overexpressed nectin recruited N-cadherin DN to the nectin-based cell-cell adhesion sites in an afadin-dependent manner. Moreover, overexpression of nectin enhanced the E-cadherin–based cell-cell adhesion activity. These results suggest that N-cadherin DN competitively inhibits the association of the endogenous nectin-afadin system with the endogenous E-cadherin-catenin system and thereby reduces the cell-cell adhesion activity of E-cadherin. Thus, nectin plays a role in the formation of E-cadherin–based AJs in keratinocytes.

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Delta-catenin promotes the proliferation and invasion of colorectal cancer cells by binding to E-cadherin in a competitive manner with p120 catenin

Targeted Oncology ◽

10.1007/s11523-013-0269-6 ◽

2013 ◽

Vol 9 (1) ◽

pp. 53-61 ◽

Cited By ~ 11

Author(s):

Hong Zhang ◽

Shun-Dong Dai ◽

Di Zhang ◽

Dong Liu ◽

Fang-Yuan Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

P120 Catenin ◽

Colorectal Cancer Cells ◽

Proliferation And Invasion ◽

E Cadherin

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Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion

Molecular Biology of the Cell ◽

10.1091/mbc.e11-12-1060 ◽

2012 ◽

Vol 23 (11) ◽

pp. 2092-2108 ◽

Cited By ~ 41

Author(s):

Yuliya I. Petrova ◽

MarthaJoy M. Spano ◽

Barry M. Gumbiner

Keyword(s):

Cell Surface ◽

Conformational Changes ◽

Binding Sites ◽

Calcium Binding ◽

Cell Types ◽

P120 Catenin ◽

Physiological Regulation ◽

Conformational Epitopes ◽

Calcium Binding Sites ◽

E Cadherin

We investigated changes in cadherin structure at the cell surface that regulate its adhesive activity. Colo 205 cells are nonadhesive cells with a full but inactive complement of E-cadherin–catenin complexes at the cell surface, but they can be triggered to adhere and form monolayers. We were able to distinguish the inactive and active states of E-cadherin at the cell surface by using a special set of monoclonal antibodies (mAbs). Another set of mAbs binds E-cadherin and strongly activates adhesion. In other epithelial cell types these activating mAbs inhibit growth factor–induced down-regulation of adhesion and epithelial morphogenesis, indicating that these phenomena are also controlled by E-cadherin activity at the cell surface. Both types of mAbs recognize conformational epitopes at different interfaces between extracellular cadherin repeat domains (ECs), especially near calcium-binding sites. Activation also induces p120-catenin dephosphorylation, as well as changes in the cadherin cytoplasmic domain. Moreover, phospho-site mutations indicate that dephosphorylation of specific Ser/Thr residues in the N-terminal domain of p120-catenin mediate adhesion activation. Thus physiological regulation of the adhesive state of E-cadherin involves physical and/or conformational changes in the EC interface regions of the ectodomain at the cell surface that are mediated by catenin-associated changes across the membrane.

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Cortical Tension Initiates the Positive Feedback Loop Between E-cadherin and F-actin

10.1101/2021.02.23.432578 ◽

2021 ◽

Author(s):

Qilin Yu ◽

William R. Holmes ◽

Jean P. Thiery ◽

Rodney B. Luwor ◽

Vijay Rajagopal

Keyword(s):

Positive Feedback ◽

Feedback Loop ◽

Adherens Junctions ◽

Force Balance ◽

Intercellular Junction ◽

Cell Junctions ◽

Positive Feedback Loop ◽

Cortical Tension ◽

E Cadherin ◽

Cell Cell

AbstractAdherens junctions (AJs) physically link two cells at their contact interface via extracellular homophilic interactions between cadherin molecules and intracellular connections between cadherins and the actomyosin cortex. Both cadherin and actomyosin cytoskeletal dynamics are reciprocally regulated by mechanical and chemical signals, which subsequently determine the strength of cell-cell adhesions and the emergent organization and stiffness of the tissues they form. However, an understanding of the integrated system is lacking. We present a new mechanistic computational model of intercellular junction maturation in a cell doublet to investigate the mechano-chemical crosstalk that regulates AJ formation and homeostasis. The model couples a 2D lattice-based model of cadherin dynamics with a continuum, reaction-diffusion model of the reorganizing actomyosin network through its regulation by Rho signaling at the intercellular junction. We demonstrate that local immobilization of cadherin induces cluster formation in a cis less dependent manner. We further investigate how cadherin and actin regulate and cooperate. By considering the force balance during AJ maturation and the force-sensitive property of the cadherin/F-actin linking molecules, we show that cortical tension applied on the contact rim can explain the ring distribution of cadherin and F-actin on the cell-cell contact of the cell-doublet. Meanwhile, the positive feedback loop between cadherin and F-actin is necessary for maintenance of the ring. Different patterns of cadherin distribution can be observed as an emergent property of disturbances of this feedback loop. We discuss these findings in light of available experimental observations on underlying mechanisms related to cadherin/F-actin binding and the mechanical environment.Significance StatementThe formation, maintenance and disassembly of adherens junctions (AJs) is fundamental to organ development, tissue integrity as well as tissue function. E-cadherins and F-actin are two major players of the adherens junctions (AJs). Although it is well known that cadherins and F-actin affect each other, how these two players work together to maintain the intercellular contact is unclear. Using a novel mechano-chemical model of E-cadherin and F-actin remodeling, we demonstrate that a positive feedback loop between cadherins and F-actin allows them to stabilize each other locally. Mechanical and chemical stimuli applied to the cell adhesion change E-cadherin and F-actin distribution by consolidating or interrupting the feedback loop locally. Our study mechanistically links mechanical force to E-cadherin patterning at cell-cell junctions.

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p120 catenin induces opposing effects on tumor cell growth depending on E-cadherin expression

The Journal of Cell Biology ◽

10.1083/jcb.200805113 ◽

2008 ◽

Vol 183 (4) ◽

pp. 737-749 ◽

Cited By ~ 63

Author(s):

Edwin Soto ◽

Masahiro Yanagisawa ◽

Laura A. Marlow ◽

John A. Copland ◽

Edith A. Perez ◽

...

Keyword(s):

Cell Growth ◽

Tumor Cell ◽

Mitogen Activated Protein Kinase ◽

Dependent Manner ◽

Tumor Cell Growth ◽

P120 Catenin ◽

Opposing Effects ◽

E Cadherin

p120 catenin regulates the activity of the Rho family guanosine triphosphatases (including RhoA and Rac1) in an adhesion-dependent manner. Through this action, p120 promotes a sessile cellular phenotype when associated with epithelial cadherin (E-cadherin) or a motile phenotype when associated with mesenchymal cadherins. In this study, we show that p120 also exerts significant and diametrically opposing effects on tumor cell growth depending on E-cadherin expression. Endogenous p120 acts to stabilize E-cadherin complexes and to actively promote the tumor-suppressive function of E-cadherin, potently inhibiting Ras activation. Upon E-cadherin loss during tumor progression, the negative regulation of Ras is relieved; under these conditions, endogenous p120 promotes transformed cell growth both in vitro and in vivo by activating a Rac1–mitogen-activated protein kinase signaling pathway normally activated by the adhesion of cells to the extracellular matrix. These data indicate that both E-cadherin and p120 are important regulators of tumor cell growth and imply roles for both proteins in chemoresistance and targeted therapeutics.

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Immunohistological Localization and Expression of α-Actin in the Baboon (Papio anubis) Corpus Luteum

Journal of Histochemistry & Cytochemistry ◽

10.1177/002215549704500110 ◽

1997 ◽

Vol 45 (1) ◽

pp. 71-77 ◽

Cited By ~ 5

Author(s):

Firyal S. Khan-Dawood ◽

Jun Yang ◽

M. Yusoff Dawood

Keyword(s):

Corpus Luteum ◽

Luteal Phase ◽

Adherens Junctions ◽

Tunica Albuginea ◽

Corpora Lutea ◽

Papio Anubis ◽

Lh Surge ◽

Luteal Cells ◽

Steroidogenic Cells ◽

E Cadherin

We have recently shown the presence of E-cadherin and of α- and γ-catenins in human and baboon corpora lutea. These are components of adherens junctions between cells. The cytoplasmic catenins link the cell membrane-associated cadherins to the actin-based cytoskeleton. This interaction is necessary for the functional activity of the E-cad-herins. Our aim therefore was to determine the presence of α-actin in the baboon corpus luteum, to further establish whether the necessary components for E-cadherin activity are present in this tissue. An antibody specific for the smooth muscle isoform of actin, α-actin, was used for these studies. The results using immunohistochemistry show that (a) α-actin is present in steroidogenic cells of the active corpus luteum, theca externa of the corpus luteum, cells of the vasculature, and the tunica albuginea surrounding the ovary. The intensity of immunoreactivity for α-actin varied, with the cells of the vasculature reacting more intensely than the luteal cells. A difference in intensity of immunoreactivity was also observed among the luteal cells, with the inner granulosa cells showing stronger immunoreactivity than the peripheral theca lutein cells. There was no detectable immunoreactivity in the steroidogenic cells of the atretic corpus luteum. However, in both the active and atretic corpora lutea, α-actin-positive vascular cells were dispersed within the tissue. (b) Total α-actin (luteal and non-luteal), as determined by Western blot analyses, does not change during the luteal phase and subsequent corpus luteum demise (atretic corpora lutea). (c) hCG stimulated the expression of α-actin and progesterone secretion by the early luteal phase (LH surge + 1–5 days) and midluteal phase (LH surge + 6–10 days) cells in culture, but only progesterone in the late luteal phase (LH surge + 11–15 days). The data show that α-actin is present in luteal cells and that its expression is regulated by hCG, thus suggesting that E-cadherin may form functional adherens junctions in the corpus luteum.

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Novel Membrane Protein shrew-1 Targets to Cadherin-Mediated Junctions in Polarized Epithelial Cells

Molecular Biology of the Cell ◽

10.1091/mbc.e03-05-0281 ◽

2004 ◽

Vol 15 (1) ◽

pp. 397-406 ◽

Cited By ~ 30

Author(s):

Sanita Bharti ◽

Heike Handrow-Metzmacher ◽

Silvia Zickenheiner ◽

Andreas Zeitvogel ◽

Rudolf Baumann ◽

...

Keyword(s):

Epithelial Cells ◽

Membrane Protein ◽

Transmembrane Protein ◽

Adherens Junctions ◽

Direct Interaction ◽

Potential Candidate ◽

Putative Open Reading Frame ◽

Polarized Epithelial Cells ◽

E Cadherin

While searching for potential candidate molecules relevant for the pathogenesis of endometriosis, we discovered a 2910-base pair cDNA encoding a novel putative 411-amino acid integral membrane protein that we called shrew-1. The putative open-reading frame was confirmed with antibodies against shrew-1 peptides that labeled a protein of ∼48 kDa in extracts of shrew-1 mRNA-positive tissue and also detected ectopically expressed shrew-1. Expression of epitope-tagged shrew-1 in epithelial cells and analysis by surface biotinylation and immunoblots demonstrated that shrew-1 is indeed a transmembrane protein. Shrew-1 is able to target to E-cadherin-mediated adherens junctions and interact with the E-cadherin–catenin complex in polarized MCF7 and Madin-Darby canine kidney cells, but not with the N-cadherin–catenin complex in nonpolarized epithelial cells. Direct interaction of shrew-1 with β-catenin in in vitro pull-down assay suggests that β-catenin might be one of the proteins that targets and/or retains shrew-1 in the adherens junctions. Interestingly, shrew-1 was partially translocated in response to scatter factor (ligand of receptor tyrosine kinase c-met) from the plasma membrane to the cytoplasm where it still colocalized with endogenous E-cadherin. In summary, we introduce shrew-1 as a novel component of adherens junctions, interacting with E-cadherin–β-catenin complexes in polarized epithelial cells.

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