scholarly journals Direct and Regulated Interaction of Integrin αEβ7 with E-Cadherin

1998 ◽  
Vol 140 (1) ◽  
pp. 197-210 ◽  
Author(s):  
Jonathan M.G. Higgins ◽  
Didier A. Mandlebrot ◽  
Sunil K. Shaw ◽  
Gary J. Russell ◽  
Elizabeth A. Murphy ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Fusion Protein ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Divalent Cations ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Vital Role ◽  
Immunoglobulin Superfamily ◽  
E Cadherin

The cadherins are a family of homophilic adhesion molecules that play a vital role in the formation of cellular junctions and in tissue morphogenesis. Members of the integrin family are also involved in cell to cell adhesion, but bind heterophilically to immunoglobulin superfamily molecules such as intracellular adhesion molecule (ICAM)–1, vascular cell adhesion molecule (VCAM)–1, or mucosal addressin cell adhesion molecule (MadCAM)–1. Recently, an interaction between epithelial (E-) cadherin and the mucosal lymphocyte integrin, αEβ7, has been proposed. Here, we demonstrate that a human E-cadherin–Fc fusion protein binds directly to soluble recombinant αEβ7, and to αEβ7 solubilized from intraepithelial T lymphocytes. Furthermore, intraepithelial lymphocytes or transfected JY′ cells expressing the αEβ7 integrin adhere strongly to purified E-cadherin–Fc coated on plastic, and the adhesion can be inhibited by antibodies to αEβ7 or E-cadherin. The binding of αEβ7 integrin to cadherins is selective since cell adhesion to P-cadherin–Fc through αEβ7 requires >100-fold more fusion protein than to E-cadherin–Fc. Although the structure of the αE-chain is unique among integrins, the avidity of αEβ7 for E-cadherin can be regulated by divalent cations or phorbol myristate acetate. Cross-linking of the T cell receptor complex on intraepithelial lymphocytes increases the avidity of αEβ7 for E-cadherin, and may provide a mechanism for the adherence and activation of lymphocytes within the epithelium in the presence of specific foreign antigen. Thus, despite its dissimilarity to known integrin ligands, the specific molecular interaction demonstrated here indicates that E-cadherin is a direct counter receptor for the αEβ7 integrin.

622: Von Hippel-Lindau Inactivation Downregulates the Cell-Cell Adhesion Molecule E Cadherin in Renal Cancer Cells

2005 ◽  
Vol 173 (4S) ◽  
pp. 170-170
Author(s):  
Maxine G. Tran ◽  
Miguel A. Esteban ◽  
Peter D. Hill ◽  
Ashish Chandra ◽  
Tim S. O'Brien ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cancer Cells ◽  
Renal Cancer ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Von Hippel Lindau ◽  
E Cadherin ◽  
Cell Cell

scholarly journals Role of Nectin in Formation of E-Cadherin–based Adherens Junctions in Keratinocytes: Analysis with the N-Cadherin Dominant Negative Mutant

2003 ◽  
Vol 14 (4) ◽  
pp. 1597-1609 ◽  
Author(s):  
Yoshinari Tanaka ◽  
Hiroyuki Nakanishi ◽  
Shigeki Kakunaga ◽  
Noriko Okabe ◽  
Tomomi Kawakatsu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Adherens Junctions ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Adhesion Activity ◽  
Negative Mutant ◽  
E Cadherin ◽  
Cell Cell

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.

scholarly journals Aberrant cell adhesion molecule expression in human bronchopulmonary sequestration and congenital cystic adenomatoid malformation

2009 ◽  
Vol 297 (1) ◽  
pp. L143-L152 ◽  
Author(s):  
MaryAnn V. Volpe ◽  
Eunice Chung ◽  
Jason P. Ulm ◽  
Brian F. Gilchrist ◽  
Steven Ralston ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Human Lung ◽  
Congenital Cystic Adenomatoid Malformation ◽  
Adhesion Molecule Expression ◽  
Protein Levels ◽  
Normal Human ◽  
Hox Protein ◽  
E Cadherin

In many organs, integrins and cadherins are partly regulated by Hox genes, but their interactions in airway morphogenesis and congenital lung diseases are unknown. We previously showed that the Hox protein HoxB5 is abnormally increased in bronchopulmonary sequestration (BPS) and congenital cystic adenomatoid malformation (CCAM), congenital lung lesions with abnormal airway branching. We now report on α2-, α3-, and β1-integrin and E-cadherin expression in normal human lung and in BPS and CCAM tissue previously shown to have abnormal HoxB5 expression and on the relationship of cell adhesion molecule expression to Hoxb5 regulation. α2-, α3-, and β1-integrins and E-cadherin expression in normal human lung and BPS and CCAM were evaluated using Western blot and immunohistochemistry. Fetal mouse lung fibroblasts with Hoxb5-specific siRNA downregulation were evaluated for α2-integrin protein levels by Western blot. Compared with normal human lung, a previously undetected α2-integrin isoform potentially lacking essential cytoplasmic sequences was significantly increased in BPS and CCAM, and α2-integrin spatial and cellular expression was more intense. E-cadherin protein levels were also significantly increased, whereas α3 increased in CCAM compared with canalicular, but not with alveolar, stage lung. β1-integrin levels were unchanged. We conclude that in BPS and CCAM, altered α2-integrin cytoplasmic signaling contributes to abnormal cellular behavior in these lung lesions. Aberrant cell adhesion molecule and Hox protein regulation are likely part of the mechanism involved in the development of BPS and CCAM.

scholarly journals Expression of cell adhesion molecule E-cadherin in Xenopus embryos begins at gastrulation and predominates in the ectoderm.

1989 ◽  
Vol 108 (6) ◽  
pp. 2449-2458 ◽  
Author(s):  
Y S Choi ◽  
B Gumbiner
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Xenopus Laevis ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Cell Layer ◽  
Outer Cell ◽  
A6 Cells ◽  
Xenopus Embryos ◽  
E Cadherin

The expression of the Ca2+-dependent epithelial cell adhesion molecule E-cadherin (also known as uvomorulin and L-CAM) in the early stages of embryonic development of Xenopus laevis was examined. E-Cadherin was identified in the Xenopus A6 epithelial cell line by antibody cross-reactivity and several biochemical characteristics. Four independent mAbs were generated against purified Xenopus E-cadherin. All four mAbs recognized the same polypeptides in A6 cells, adult epithelial tissues, and embryos. These mAbs inhibited the formation of cell contacts between A6 cells and stained the basolateral plasma membranes of A6 cells, hepatocytes, and alveolar epithelial cells. The time of E-cadherin expression in early Xenopus embryos was determined by immunoblotting. Unlike its expression in early mouse embryos, E-cadherin was not present in the eggs or early blastula of Xenopus laevis. These findings indicate that a different Ca2+-dependent cell adhesion molecule, perhaps another member of the cadherin gene family, is responsible for the Ca2+-dependent adhesion between cleavage stage Xenopus blastomeres. Detectable accumulation of E-cadherin started just before gastrulation at stage 9 1/2 and increased rapidly up to the end of gastrulation at stage 15. In stage 15 embryos, specific immunofluorescence staining of E-cadherin was discernible only in ectoderm, but not in mesoderm and endoderm. The ectoderm at this stage consists of two cell layers. The outer cell layer of ectoderm was stained intensely, and staining was localized to the basolateral plasma membrane of these cells. Lower levels of staining were observed in the inner cell layer of ectoderm. The coincidence of E-cadherin expression with the process of gastrulation and its restriction to the ectoderm indicate that it may play a role in the morphogenetic movements of gastrulation and resulting segregation of embryonic germ layers.

Axonal cell-adhesion molecule L1 in CNS myelination

2004 ◽  
Vol 1 (1) ◽  
pp. 65-72 ◽  
Author(s):  
G. BARBIN ◽  
M.S. AIGROT ◽  
P. CHARLES ◽  
A. FOUCHER ◽  
M. GRUMET ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Culture Medium ◽  
Immunoglobulin Superfamily ◽  
Map Kinase Pathway ◽  
Cell Adhesion Molecule L1 ◽  
Cns Myelination ◽  
Kinase Pathway

Of the axonal signals influencing myelination, adhesion molecules expressed at the axonal surface are strong candidates to mediate interactions between myelinating cells and axons. The recognition cell-adhesion molecule L1, a member of the immunoglobulin superfamily has been shown to play important roles in neuronal migration and survival, and in PNS myelination. We have investigated the role of axonally expressed L1 in CNS myelination. In co-cultures of myelinating oligodendrocytes and neurons derived from murine brain, we demonstrate that, before myelination, L1 immunoreactivity is confined to neurites. After myelination commences, L1 expression is downregulated on myelinated axons and adjacent, but not yet myelinated, internodes. Interfering with L1 before the onset of myelination, by adding either anti-L1 antibody or L1-Fc fusion proteins to the culture medium, inhibits myelination. In addition, in purified cultures of oligodendrocytes, L1-Fc fusion protein prevents lysophosphatidic acid-induced activation of the mitogen-activated kinase (MAP)-kinase pathway. Together, our data indicate that L1 is involved in the initiation of CNS myelination, and that this effect might involve the dephosphorylation of oligodendroglial phosphoproteins.

scholarly journals A Label-Free Approach to Identify Inhibitors of α4β7-Mediated Cell Adhesion to MadCAM

2011 ◽  
Vol 16 (5) ◽  
pp. 536-544 ◽  
Author(s):  
Michael P. Bova ◽  
Lan Nguyen ◽  
William Wallace ◽  
Caroline Garrido ◽  
Ying-Zi Xu ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
High Throughput Screening ◽  
Cell Adhesion Molecule ◽  
Divalent Cations ◽  
Jurkat Cells ◽  
Label Free ◽  
Blocking Antibody ◽  
Assay Format ◽  
Homogeneous Assay

Traditionally, cell adhesion assays are performed in a manual workstation format using fluorescence-based readouts. Herein, the authors describe a label-free homogeneous assay to identify inhibitors of α4β7 integrin-mediated cell adhesion to its ligand, the mucosal addressin cell adhesion molecule (MadCAM), using the SRU BIND platform. The biosensor is optically based and comprises a subwavelength polymer grating. The assay was validated using standard compounds and an α4 blocking antibody and correlated very closely with the manual assay format when running a battery of test compounds of varying potencies. Cell adhesion was strictly dependent on the presence of divalent cations where Mg2+ was greater than Ca2+ at promoting cell adhesion. This homogeneous and label-free format exhibited low variability with a calculated Z′ of 0.6. In addition to measuring α4β7-mediated 8866 cell adhesion to MadCAM, the authors also demonstrate that this platform can measure adhesion of Jurkat cells expressing α4β1 to the vascular cell adhesion molecule. Thus, the SRU BIND platform is widely applicable to measuring cell adhesion events mediated by other integrins binding to their receptors in an assay format that is amenable to high-throughput screening.

Mechanisms of monozygotic (MZ) twinning: A possible role for the cell adhesion molecule, E-cadherin

2003 ◽  
Vol 120A (1) ◽  
pp. 59-62 ◽  
Author(s):  
Fiona Bamforth ◽  
Lindsay Brown ◽  
Janine Senz ◽  
David Huntsman
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
E Cadherin
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