Epithelial Cells
Bruce S. Bochner in Adhesion Molecules in Allergic Disease, 2020
The cadherins are a group of calcium-dependent cell-surface adhesion molecules that mediate cell–cell adhesion. They are made up of a single polypeptide chain and engage in homophilic adhesion of one cadherin molecule to another on an opposing cell membrane (60). Epithelial cadherin (E-cadherin, also called uvomorulin, Arc-1, liver cell adhesion molecule, L-CAM, and cell CAM 120/80) has been identified as a constituent of intermediate junctions in the bronchial epithelium. It localizes by immunofluorescence to the lateral cell membrane close to the luminal surface (45). Recent determination of the solution structure of E-cadherin revealed unexpected structural similarities to the immunoglobulin fold. The molecule has seven β-strands arranged in a “β-barrer topology, and two short α-helices, one of which provides the calcium-binding pocket. The putative adhesion interface is centered around the F-strand of the β-sheet and contains a conserved His-Ala-Val sequence (81). E-cadherin has been implicated in the suppression of tumor invasiveness, as its expression is decreased in the invasive phase of epithelial malignancies (82–84).
Cell Components and Function
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2020
Most cells except for red blood cells have integral membrane proteins that attach to the extracellular matrix or with adhesion molecules on neighbouring cells. These molecules hold the tissue together and permit the transmission of mechanical forces from one cell to another. Some also act as receptors. The integrins are cell-matrix adhesion molecules that link cells to fibronectin or laminin in the extracellular matrix. The cadherins are glycoproteins that mediate Ca-dependent cell–cell adhesion. They bind to a copy of the molecule to cadherins on the other molecule. Intercellular adhesion molecules (ICAMS) are expressed on capillary endothelial cell surfaces that are activated by infection of surrounding tissue. They bind to integrins on white cells and promote their movement to sites of infection. Selectins are carbohydrate binding proteins on endothelial cell membranes that recognize sugars on white blood cell surfaces and form the initial binding, which is strengthened by ICAMs.
Transitional Cell Carcinoma of the Bladder
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
Cadherins are the main mediators of cell-cell adhesion in epithelial tissues, being major components of both the adherens junction and desmosomes. Adhesion is achieved by homodimeric interactions between the extracellular domains of classical cadherins (E-cadherin, P-cadherin, and N-cadherin) on neighboring cells. Catenins (α-, β-, and γ-catenin and p120) anchor the cadherins to the cell cytoskeleton. In bladder TCC, reduced E-cadherin and β-catenin expression is associated with high grade and stage. Although E-cadherin has been shown to be an independent prognostic factor on multivariate analysis (65), many other studies have disputed its independent prognostic value for progression. Mutations, hypermethylation, and transcriptional repression of the E-cadherin gene may play a role in reduced expression.
Expression of N-cadherin and β-catenin in human meningioma in correlation with peritumoral edema
Published in International Journal of Neuroscience, 2018
Robert Rutkowski, Robert Chrzanowski, Magdalena Trwoga, Jan Kochanowicz, Grzegorz Turek, Zenon Mariak, Joanna Reszeć
Cadherins are a family of glycoproteins that are associated with cell adhesion mechanisms. In humans, there are more than 80 proteins belonging to the cadherin family, like E- and P-cadherins which are regarded as the epithelial subtype. Cadherins are composed of an extracellular part that mediates calcium-dependent interactions between cadherins and a transmembrane and cytoplasmic part [4]. Many data show that the alterations between the intercellular reactions, the expression and function of cell-cell and cell-matrix proteins expression are associated with progression to the malignancy [5]. E-cadherin is known to be expressed in most of the epithelial neoplasms, including meningiomas. In most of the data concerning low-grade meningiomas, the researchers presented a significant E-cadherin expression. Schwechheimer et al. showed a significant E-cadherin expression in all of the examined meningiomas regardless of the histomorphological subtypes [5,6]. However, E-cadherin expression is lost in many types of the carcinomas, including breast cancer or colorectal cancer [7,8].
AMPK in regulation of apical junctions and barrier function of intestinal epithelium
Published in Tissue Barriers, 2018
Mei-Jun Zhu, Xiaofei Sun, Min Du
The cadherin superfamily contains of more than 20 members. Of these, epithelial cadherin (E-cadherin) is the most prominent in epithelial tissues and has a vital role in epithelial cell AJs assembly. The extracellular domain of E-cadherin contains five repetitive domains or cadherin repeats. Each cadherin repeat has a calcium-binding domain.58 In the presence of calcium, E-cadherin interacts with other E-cadherins of the same or opposed cells through respective extracellular domains.59 The cytoplasmic region of cadherin interacts with catenins and forms the cadherins-catenins complex, which then binds to actin microfilament (Fig. 2).60 Similar to cadherins, nectins have a single transmembrane domain and interact with each other through an extracellular domain.61 The Inter-cellular interaction of nectins is not dependent on Ca2+. Cytoplasmic tails of nectins interact with afadins through their PDZ binding motifs, which further associate with actin filaments (Fig. 2).62 Nectins cooperate with cadherins in generating functional AJs.57
Cell-cell junctions: structure and regulation in physiology and pathology
Published in Tissue Barriers, 2021
Mir S. Adil, S. Priya Narayanan, Payaningal R. Somanath
AJs are primarily made up of cadherin–catenin protein complexes, which are linked to the actin cytoskeleton.40 While cadherins make the transmembrane protein part, plaque proteins are made up of catenins, plakoglobin, p120, and others.31 Over 170 proteins have been reported to colocalize with cadherin or catenins in AJs, and either directly interact with them or affect AJ dynamics.41 Cadherins are transmembrane, calcium-dependent membrane proteins8,41–43 that have an ectodomain consisting of five cadherin motifs and a cytoplasmic domain with two conserved motifs.42 They form antiparallel homotypic adhesive complexes with adjacent cells after dimerization and clustering.40,41,44 They are essential proteins for morphogenesis and tissue homeostasis.45 Cadherins regulate the plasticity and control the passage of solutes, water, and lymphoid cells across the cell layer through epithelial and endothelial cell junctions.46 The superfamily of transmembrane cadherin proteins is comprised of more than 100 members in humans, including other classical cadherins, numerous proto-cadherins, and cadherin-related proteins.47 Several tissue-specific cadherins have been identified, including epithelial (E)-cadherin, neuronal (N)-cadherin, placental (P)-cadherin, vascular endothelial (VE)- cadherin, and others.8 Disruption in the expression or function of such individual cadherins results in abnormal development of the respective organs.41
Related Knowledge Centers
- Adherens Junction
- Calcium
- Cell Adhesion Molecule
- Desmocollin
- Desmoglein
- Transmembrane Protein
- Ion
- Cadherin Cytoplasmic Region
- Adhesome
- Protocadherin