scholarly journals A molecular mechanism directly linking E-cadherin adhesion to initiation of epithelial cell surface polarity

2007 ◽  
Vol 178 (2) ◽  
pp. 323-335 ◽  
Author(s):  
Lene N. Nejsum ◽  
W. James Nelson
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Cell Surface ◽  
Basolateral Membrane ◽  
Surface Polarity ◽  
Cell Contacts ◽  
Protein Receptors ◽  
Epithelial Cell Surface ◽  
E Cadherin ◽  
Cell Cell

Mechanisms involved in maintaining plasma membrane domains in fully polarized epithelial cells are known, but when and how directed protein sorting and trafficking occur to initiate cell surface polarity are not. We tested whether establishment of the basolateral membrane domain and E-cadherin–mediated epithelial cell–cell adhesion are mechanistically linked. We show that the basolateral membrane aquaporin (AQP)-3, but not the equivalent apical membrane AQP5, is delivered in post-Golgi structures directly to forming cell–cell contacts where it co-accumulates precisely with E-cadherin. Functional disruption of individual components of a putative lateral targeting patch (e.g., microtubules, the exocyst, and soluble N-ethylmaleimide–sensitive factor attachment protein receptors) did not inhibit cell–cell adhesion or colocalization of the other components with E-cadherin, but each blocked AQP3 delivery to forming cell–cell contacts. Thus, components of the lateral targeting patch localize independently of each other to cell–cell contacts but collectively function as a holocomplex to specify basolateral vesicle delivery to nascent cell–cell contacts and immediately initiate cell surface polarity.

scholarly journals Remodeling the cell surface distribution of membrane proteins during the development of epithelial cell polarity.

1992 ◽  
Vol 116 (4) ◽  
pp. 889-899 ◽  
Author(s):  
D A Wollner ◽  
K A Krzeminski ◽  
W J Nelson
Keyword(s):  
Epithelial Cell ◽  
Membrane Proteins ◽  
Cell Surface ◽  
Mdck Cells ◽  
Apical Cell ◽  
Cell Contact ◽  
Surface Polarity ◽  
Lateral Membrane ◽  
E Cadherin ◽  
Cell Cell

The development of polarized epithelial cells from unpolarized precursor cells follows induction of cell-cell contacts and requires resorting of proteins into different membrane domains. We show that in MDCK cells the distributions of two membrane proteins, Dg-1 and E-cadherin, become restricted to the basal-lateral membrane domain within 8 h of cell-cell contact. During this time, however, 60-80% of newly synthesized Dg-1 and E-cadherin is delivered directly to the forming apical membrane and then rapidly removed, while the remainder is delivered to the basal-lateral membrane and has a longer residence time. Direct delivery of greater than 95% of these proteins from the Golgi complex to the basal-lateral membrane occurs greater than 48 h later. In contrast, we show that two apical proteins are efficiently delivered and restricted to the apical cell surface within 2 h after cell-cell contact. These results provide insight into mechanisms involved in the development of epithelial cell surface polarity, and the establishment of protein sorting pathways in polarized cells.

scholarly journals Plasticity in epithelial cell phenotype: modulation by expression of different cadherin cell adhesion molecules.

1995 ◽  
Vol 129 (2) ◽  
pp. 507-519 ◽  
Author(s):  
J A Marrs ◽  
C Andersson-Fisone ◽  
M C Jeong ◽  
L Cohen-Gould ◽  
C Zurzolo ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Apical Membrane ◽  
Retinal Pigment ◽  
Cell Phenotype ◽  
Cell Contacts ◽  
Membrane Cytoskeleton ◽  
E Cadherin ◽  
Cell Cell

A primary function of cadherins is to regulate cell adhesion. Here, we demonstrate a broader function of cadherins in the differentiation of specialized epithelial cell phenotypes. In situ, the rat retinal pigment epithelium (RPE) forms cell-cell contacts within its monolayer, and at the apical membrane with the neural retina; Na+, K(+)-ATPase and the membrane cytoskeleton are restricted to the apical membrane. In vitro, RPE cells (RPE-J cell line) express an endogenous cadherin, form adherens junctions and a tight monolayer, but Na+,K(+)-ATPase is localized to both apical and basal-lateral membranes. Expression of E-cadherin in RPE-J cells results in restriction and accumulation of both Na+,K(+)-ATPase and the membrane cytoskeleton at the lateral membrane; these changes correlate with the synthesis of a different ankyrin isoform. In contrast to both RPE in situ and RPE-J cells that do not form desmosomes, E-cadherin expression in RPE-J cells induces accumulation of desmoglein mRNA, and assembly of desmosome-keratin complexes at cell-cell contacts. These results demonstrate that cadherins directly affect epithelial cell phenotype by remodeling the distributions of constitutively expressed proteins and by induced accumulation of specific proteins, which together lead to the generation of structurally and functionally distinct epithelial cell types.

scholarly journals Keratin 19 maintains E-cadherin localization at the cell surface and stabilizes cell-cell adhesion of MCF7 cells

2021 ◽  
Vol 15 (1) ◽  
pp. 1-17
Author(s):  
Sarah Alsharif ◽  
Pooja Sharma ◽  
Karina Bursch ◽  
Rachel Milliken ◽  
Van Lam ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Mcf7 Cells ◽  
Keratin 19 ◽  
E Cadherin ◽  
Cell Cell

scholarly journals RAC1 Regulates Adherens Junctions through Endocytosis of E-Cadherin

2001 ◽  
Vol 12 (4) ◽  
pp. 847-862 ◽  
Author(s):  
Nasreen Akhtar ◽  
Neil A. Hotchin
Keyword(s):  
Cell Adhesion ◽  
Fluorescent Protein ◽  
Adherens Junctions ◽  
Expression Vectors ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Cell Contacts ◽  
Green Fluorescent ◽  
E Cadherin ◽  
Cell Cell

The establishment of cadherin-dependent cell–cell contacts in human epidermal keratinocytes are known to be regulated by the Rac1 small GTP-binding protein, although the mechanisms by which Rac1 participates in the assembly or disruption of cell–cell adhesion are not well understood. In this study we utilized green fluorescent protein (GFP)-tagged Rac1 expression vectors to examine the subcellular distribution of Rac1 and its effects on E-cadherin–mediated cell–cell adhesion. Microinjection of keratinocytes with constitutively active Rac1 resulted in cell spreading and disruption of cell–cell contacts. The ability of Rac1 to disrupt cell–cell adhesion was dependent on colony size, with large established colonies being resistant to the effects of active Rac1. Disruption of cell–cell contacts in small preconfluent colonies was achieved through the selective recruitment of E-cadherin–catenin complexes to the perimeter of multiple large intracellular vesicles, which were bounded by GFP-tagged L61Rac1. Similar vesicles were observed in noninjected keratinocytes when cell–cell adhesion was disrupted by removal of extracellular calcium or with the use of an E-cadherin blocking antibody. Moreover, formation of these structures in noninjected keratinocytes was dependent on endogenous Rac1 activity. Expression of GFP-tagged effector mutants of Rac1 in keratinocytes demonstrated that reorganization of the actin cytoskeleton was important for vesicle formation. Characterization of these Rac1-induced vesicles revealed that they were endosomal in nature and tightly colocalized with the transferrin receptor, a marker for recycling endosomes. Expression of GFP-L61Rac1 inhibited uptake of transferrin-biotin, suggesting that the endocytosis of E-cadherin was a clathrin-independent mechanism. This was supported by the observation that caveolin, but not clathrin, localized around these structures. Furthermore, an inhibitory form of dynamin, known to inhibit internalization of caveolae, inhibited formation of cadherin vesicles. Our data suggest that Rac1 regulates adherens junctions via clathrin independent endocytosis of E-cadherin.

scholarly journals Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin.

1992 ◽  
Vol 118 (3) ◽  
pp. 671-679 ◽  
Author(s):  
K A Knudsen ◽  
M J Wheelock
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Molecular Mass ◽  
Beta Catenin ◽  
Calcium Dependent ◽  
Intracellular Proteins ◽  
Dependent Cell ◽  
Cell Surface Glycoproteins ◽  
E Cadherin ◽  
Cell Cell

E- and N-cadherin are members of a family of calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. Extracellularly, the transmembrane cadherins self-associate, while, intracellularly, they interact with the actin-based cytoskeleton. Several intracellular proteins, collectively termed catenins, have been noted to co-immunoprecipitate with E- and N-cadherin and are thought to be involved in linking the cadherins to the cytoskeleton. Two catenins have been identified recently: a 102-kD vinculin-like protein (alpha-catenin) and a 92-kD Drosophila armadillo/plakoglobin-like protein (beta-catenin). Here, we show that plakoglobin, or an 83-kD plakoglobin-like protein, co-immunoprecipitates and colocalizes with both E- and N-cadherin. The 83-kD protein is immunologically distinct from the 92-kD beta-catenin and, because of its molecular mass, likely represents the cadherin-associated protein called gamma-catenin. Thus, two different members of a plakoglobin family associate with N- and E-cadherin and, together with the 102-kD alpha-catenin, appear to participate in linking the cadherins to the actin-based cytoskeleton.

scholarly journals CD151 regulates epithelial cell–cell adhesion through PKC- and Cdc42-dependent actin cytoskeletal reorganization

2003 ◽  
Vol 163 (1) ◽  
pp. 165-176 ◽  
Author(s):  
Masaki Shigeta ◽  
Noriko Sanzen ◽  
Masayuki Ozawa ◽  
Jianguo Gu ◽  
Hitoshi Hasegawa ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
Cytoskeletal Reorganization ◽  
Cortical Actin ◽  
A431 Cells ◽  
Kinase C ◽  
Integrin Α3β1 ◽  
E Cadherin ◽  
Cell Cell

CD151, a member of the tetraspanin family proteins, tightly associates with integrin α3β1 and localizes at basolateral surfaces of epithelial cells. We found that overexpression of CD151 in A431 cells accelerated intercellular adhesion, whereas treatment of cells with anti-CD151 mAb perturbed the integrity of cortical actin filaments and cell polarity. E-Cadherin puncta formation, indicative of filopodia-based adhesion zipper formation, as well as E-cadherin anchorage to detergent-insoluble cytoskeletal matrix, was enhanced in CD151-overexpressing cells. Levels of GTP-bound Cdc42 and Rac were also elevated in CD151-overexpressing cells, suggesting the role of CD151 in E-cadherin–mediated cell–cell adhesion as a modulator of actin cytoskeletal reorganization. Consistent with this possibility, engagement of CD151 by the substrate-adsorbed anti-CD151 mAb induced prominent Cdc42-dependent filopodial extension, which along with E-cadherin puncta formation, was strongly inhibited by calphostin C, a protein kinase C (PKC) inhibitor. Together, these results indicate that CD151 is involved in epithelial cell–cell adhesion as a modulator of PKC- and Cdc42-dependent actin cytoskeletal reorganization.

scholarly journals Rack1 promotes epithelial cell–cell adhesion by regulating E-cadherin endocytosis

Oncogene ◽  
2011 ◽  
Vol 31 (3) ◽  
pp. 376-389 ◽  
Author(s):  
G Swaminathan ◽  
C A Cartwright
Keyword(s):  
Cell Adhesion ◽  
Epithelial Cell ◽  
E Cadherin ◽  
Cell Cell
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