scholarly journals Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion.

1993 ◽  
Vol 123 (6) ◽  
pp. 1857-1865 ◽  
Author(s):  
R S Bradley ◽  
P Cowin ◽  
A M Brown
Keyword(s):  
Cell Adhesion ◽  
Pc12 Cells ◽  
Morphological Changes ◽  
Fetal Brain ◽  
Cell Types ◽  
Cellular Adhesion ◽  
Signaling Mechanism ◽  
Calcium Dependent ◽  
Junction Protein ◽  
E Cadherin

The Wnt-1 gene plays an essential role in fetal brain development and encodes a secreted protein whose signaling mechanism is presently unknown. In this report we have investigated intracellular mechanisms by which the Wnt-1 gene induces morphological changes in PC12 pheochromocytoma cells. PC12 cells expressing Wnt-1 show increased steady-state levels of the adhesive junction protein plakoglobin, and an altered distribution of this protein within the cell. This effect appears similar to a modulation of the plakoglobin homolog, Armadillo, that occurs in Drosophila embryos in response to the Wnt-1 homolog, wingless (Riggleman, B., P. Schedl, and E. Wieschaus. 1990. Cell. 63:549-560). In addition, PC12/Wnt-1 cells show elevated expression of E-cadherin and increased calcium-dependent cell-cell adhesion. These results imply evolutionary conservation of cellular responses to Wnt-1/wingless and indicate that in certain cell types Wnt-1 may act to modulate cell adhesion mechanisms.

Enhanced E-cadherin expression and increased calcium-dependent cell-cell adhesion in human T-cell leukemia virus type I Tax-expressing PC12 cells

1996 ◽  
Vol 109 (3) ◽  
pp. 609-617 ◽  
Author(s):  
I. Kitajima ◽  
K. Kawahara ◽  
N. Hanyu ◽  
H. Shin ◽  
T. Tokioka ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Pc12 Cells ◽  
Type I ◽  
Cell Leukemia Virus Type ◽  
Calcium Dependent ◽  
Tax Protein ◽  
Human T Cell ◽  
Dependent Cell ◽  
E Cadherin ◽  
Cell Cell

Human T-cell leukemia virus type I (HTLV-I) Tax protein induces the expression of host cellular genes, some of which are crucial in cell proliferation and differentiation. We examined the mechanisms by which HTLV-I Tax protein induces phenotypic changes in PC12 cells. We demonstrated that the HTLV-I Tax gene induces epithelioid changes and increases cell-cell contact in PC12 cells. No change in the expression of the neural cell adhesion molecule was observed between HTLV-I Tax-expressing PC12 cells and PC12 cells transfected with a control plasmid. However, HTLV-I Tax-expressing PC12 cells demonstrated a marked change in the abundance and distribution of E-cadherin, which was concentrated at regions of cellular contact and accompanied by changes in calcium-dependent cell adhesion. Although E-cadherin is expressed at low levels in PC12 and PC12 transfected with a control plasmid cells, the steady state level of E-cadherin in tax-expressing PC12 cells increases significantly, apparently as a result of regulation at the transcriptional level. Diminished expression of Tax protein in Tax-expressing PC12 cells exposed to antisense oligonucleotides for the Tax gene suppresses E-cadherin expression and decreases cell-cell adhesion. These findings imply that HTLV-I Tax protein enhanced E-cadherin expression modulates calcium-dependent cell-cell adhesion mechanisms.

Mislocalization of Adherens Junction- Associated Proteins in a Patient with Darier Disease

2018 ◽  
Vol 2 (3) ◽  
pp. 184-201
Author(s):  
George D Glinos ◽  
Irena Pastar ◽  
Marjana Tomic-Canic ◽  
Rivka C Stone
Keyword(s):  
Adherens Junction ◽  
Cellular Adhesion ◽  
Calcium Flux ◽  
Keratinocyte Differentiation ◽  
Calcium Dependent ◽  
Endoplasmic Reticulum Calcium ◽  
Darier Disease ◽  
Associated Proteins ◽  
Attachment Proteins ◽  
E Cadherin

Darier disease (DD) is an autosomal dominant keratinizing genodermatosis that manifests clinically with red-brown pruritic papules in a seborrheic distribution often in association with palmoplantar pits and dystrophic nail changes. It is caused by mutation in ATP2A2 which encodes a sarco/endoplasmic reticulum calcium ATPase isoform 2 (SERCA2) pump that regulates calcium flux. Consequent alteration of intracellular calcium homeostasis is thought to impair trafficking of cellular adhesion proteins and to lead to aberrant keratinocyte differentiation, contributing to the characteristic histopathologic features of acantholysis and dyskeratosis in DD, though the precise mechanisms are incompletely understood. Previous studies have identified defective localization of desmosomal attachment proteins in skin biopsies and cultured keratinocytes from DD patients, but reports of effects on adherens junction proteins (including calcium-dependent E-cadherin) are conflicting. Here we describe a case of DD presenting with characteristic clinical and histologic features in which we performed immunofluorescence staining of four adherens junction-associated proteins (E-cadherin, α-catenin, β-catenin, and vinculin). In lesional (acantholytic) DD skin, we identified loss of distinctive bright membranous staining that was present at the periphery of keratinocytes throughout the epidermis in the healthy skin of a matched donor. Perilesional (non-acantholytic) portions of DD skin partially recapitulated the normal phenotype. Our findings support a role for SERCA2 dysfunction in impaired assembly of adherens junctions, which together with defective desmosomes contribute to acantholysis in DD.

scholarly journals Calcium-dependent cell-cell adhesion molecules common to hepatocytes and teratocarcinoma stem cells.

1983 ◽  
Vol 97 (3) ◽  
pp. 944-948 ◽  
Author(s):  
S I Ogou ◽  
C Yoshida-Noro ◽  
M Takeichi
Keyword(s):  
Stem Cells ◽  
Cell Adhesion ◽  
Cell Types ◽  
Surface Proteins ◽  
Calcium Dependent ◽  
Molecular Weights ◽  
Teratocarcinoma Cells ◽  
Dependent Cell ◽  
Molecular Constitution ◽  
Cell Cell

The molecules involved in Ca2+-dependent cell-cell adhesion systems (CDS) in mouse hepatocytes were characterized and compared with those in teratocarcinoma cells. Fab fragments of antibody raised against liver tissues (anti-liver) inhibited Ca2+-dependent aggregation of both liver and teratocarcinoma cells. A monoclonal antibody raised against teratocarcinoma CDS (ECCD-1) also inhibited the Ca2+-dependent aggregation of these two cell types equally. These antibodies induced disruption of cell-cell adhesion in monolayers of hepatocytes. Thus, CDS in these two cell types are not immunologically distinctive. Immunochemical analyses with these antibodies showed that CDS in both hepatocytes and teratocarcinoma cells involved at least two classes of cell surface proteins with molecular weights of 124,000 and 104,000. ECCD-1 selectively bound to hepatocytes but not to fibroblastic cells in liver cell cultures. Thus, the molecular constitution of CDS in hepatocytes and teratocarcinoma stem cells is identical. As ECCD-1 reacts with other classes of embryonic and fetal cells, the molecules identified here could have a major role in cell-cell adhesion in various tissues at any developmental stage of animals.

scholarly journals Structure-Based Virtual Screening Allows the Identification of Efficient Modulators of E-Cadherin-Mediated Cell–Cell Adhesion

2019 ◽  
Vol 20 (14) ◽  
pp. 3404 ◽  
Author(s):  
Andrea Dalle Vedove ◽  
Federico Falchi ◽  
Stefano Donini ◽  
Aurelie Dobric ◽  
Sebastien Germain ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Virtual Screening ◽  
Adherens Junction ◽  
Large Family ◽  
Calcium Dependent ◽  
Molecule Inhibitor ◽  
Dependent Cell ◽  
Cell Adhesion Proteins ◽  
E Cadherin ◽  
Cell Cell

Cadherins are a large family of transmembrane calcium-dependent cell adhesion proteins that orchestrate adherens junction formation and are crucially involved in tissue morphogenesis. Due to their important role in cancer development and metastasis, cadherins can be considered attractive targets for drug discovery. A recent crystal structure of the complex of a cadherin extracellular portion and a small molecule inhibitor allowed the identification of a druggable interface, thus providing a viable strategy for the design of cadherin dimerization modulators. Here, we report on a structure-based virtual screening approach that led to the identification of efficient and selective modulators of E-cadherin-mediated cell–cell adhesion. Of all the putative inhibitors that were identified and experimentally tested by cell adhesion assays using human pancreatic tumor BxPC-3 cells expressing both E-cadherin and P-cadherin, two compounds turned out to be effective in inhibiting stable cell–cell adhesion at micromolar concentrations. Moreover, at the same concentrations, one of them also showed anti-invasive properties in cell invasion assays. These results will allow further development of novel and selective cadherin-mediated cell–cell adhesion modulators for the treatment of a variety of cadherin-expressing solid tumors and for improving the efficiency of drug delivery across biological barriers.

scholarly journals Regulation of C-cadherin function during activin induced morphogenesis of Xenopus animal caps.

1994 ◽  
Vol 126 (2) ◽  
pp. 519-527 ◽  
Author(s):  
W M Brieher ◽  
B M Gumbiner
Keyword(s):  
Cell Adhesion ◽  
Single Cells ◽  
Cell Types ◽  
Aggregation Assay ◽  
Animal Pole ◽  
Mesodermal Cell ◽  
Calcium Dependent ◽  
L Cells ◽  
Steady State Levels ◽  
Cell Cell

Treatment of Xenopus animal pole tissue with activin results in the induction of mesodermal cell types and a dramatic elongation of the tissue. The morphogenetic movements involved in the elongation appear similar to those in normal gastrulation, which is driven by cell rearrangement and cell intercalations. We have used this system to explore the potential regulation of cell-cell adhesion and cadherin function during morphogenesis. Quantitative blastomere aggregation assays revealed that activin induction reduced the calcium-dependent adhesion between blastomeres. Activin-induced blastomeres formed smaller aggregates, and a greater proportion of the population remained as single cells compared to uninduced blastomeres. The aggregation was mediated by C-cadherin because C-cadherin was present in the blastomeres during the aggregation assay, and monoclonal antibodies against C-cadherin inhibited the calcium-dependent aggregation of blastomeres. E-cadherin was not detectable until after the completion of the assay and, therefore, does not explain the adhesive differences between induced and uninduced blastomeres. L cells stably expressing C-cadherin (LC cells) were used to demonstrate that C-cadherin activity was specifically altered after activin induction. Blastomeres induced with activin bound fewer LC cells than uninduced blastomers. L cells not expressing C-cadherin did not adhere to blastomeres. The changes in C-cadherin-mediated adhesion occurred without detectable changes in the steady-state levels of C-cadherin or the amount of C-cadherin present on the surface of the cell. Immunoprecipitation of C-cadherin and its associated catenins revealed that the ratio of C-cadherin and the catenins was not altered by activin induction. These results demonstrate that activin decreases the adhesive function of existing C-cadherin molecules on the surface of blastomeres and suggest that decreased cadherin mediated cell-cell adhesion is associated with increased morphogenetic movement.

scholarly journals Small GTPase RhoG Is a Key Regulator for Neurite Outgrowth in PC12 Cells

2000 ◽  
Vol 20 (19) ◽  
pp. 7378-7387 ◽  
Author(s):  
Hironori Katoh ◽  
Hidekazu Yasui ◽  
Yoshiaki Yamaguchi ◽  
Junko Aoki ◽  
Hirotada Fujita ◽  
...  
Keyword(s):  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Morphological Changes ◽  
Cell Types ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Dominant Negative ◽  
Wild Type ◽  
Rho Family ◽  
Constitutively Active

ABSTRACT The Rho family of small GTPases has been implicated in cytoskeletal reorganization and subsequent morphological changes in various cell types. Among them, Rac and Cdc42 have been shown to be involved in neurite outgrowth in neuronal cells. In this study, we examined the role of RhoG, another member of Rho family GTPases, in nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells. Expression of wild-type RhoG in PC12 cells induced neurite outgrowth in the absence of NGF, and the morphology of wild-type RhoG-expressing cells was similar to that of NGF-differentiated cells. Constitutively active RhoG-transfected cells extended short neurites but developed large lamellipodial or filopodial structures at the tips of neurites. RhoG-induced neurite outgrowth was inhibited by coexpression with dominant-negative Rac1 or Cdc42. In addition, expression of constitutively active RhoG elevated endogenous Rac1 and Cdc42 activities. We also found that the NGF-induced neurite outgrowth was enhanced by expression of wild-type RhoG whereas expression of dominant-negative RhoG suppressed the neurite outgrowth. Furthermore, constitutively active Ras-induced neurite outgrowth was also suppressed by dominant-negative RhoG. Taken together, these results suggest that RhoG is a key regulator in NGF-induced neurite outgrowth, acting downstream of Ras and upstream of Rac1 and Cdc42 in PC12 cells.

Differential expression of cell-cell adhesion proteins and cyclin D in MEK1-transdifferentiated MDCK cells

2000 ◽  
Vol 279 (5) ◽  
pp. C1472-C1482 ◽  
Author(s):  
Ingrid Marschitz ◽  
Judith Lechner ◽  
Irene Mosser ◽  
Martina Dander ◽  
Roberto Montesano ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Adhesion ◽  
Mdck Cells ◽  
Cell Types ◽  
Mek Inhibitor ◽  
Mitogen Activated Protein Kinase ◽  
Cyclin D ◽  
Invasive Phenotype ◽  
E Cadherin ◽  
Cell Cell

Overexpression of a constitutively active mutant of the mitogen-activated protein kinase kinase MEK1 (caMEK1) in epithelial Madin-Darby canine kidney (MDCK)-C7 cells disrupts morphogenesis, induces an invasive phenotype, and is associated with a reduced rate of cell proliferation. The role of cell-cell adhesion molecules and cell cycle proteins in these processes, however, has not been investigated. We now report loss of E-cadherin expression as well as a marked reduction of β- and α-catenin expression in transdifferentiated MDCK-C7 cells stably expressing caMEK1 (C7caMEK1) compared with epithelial mock-transfected MDCK-C7 (C7Mock1) cells. At least part of the remaining α-catenin was coimmunoprecipitated with β-catenin, whereas no E-cadherin was detected in β-catenin immunoprecipitates. In both cell types, the proteasome-specific protease inhibitors N-acetyl-Leu-Leu-norleucinal (ALLN) and lactacystin led to a time-dependent accumulation of β-catenin, including the appearance of high-molecular-weight β-catenin species. Quiescent as well as serum-stimulated C7caMEK1 cells showed a higher cyclin D expression than epithelial C7Mock1 cells. The MEK inhibitor U-0126 inhibited extracellular signal-regulated kinase phosphorylation and cyclin D expression in C7caMEK1 cells and almost abolished their already reduced cell proliferation rate. We conclude that the transdifferentiated and invasive phenotype of C7caMEK1 cells is associated with a diminished expression of proteins involved in cell-cell adhesion. Although β-catenin expression is reduced, C7caMEK1 cells show a higher expression of U-0126-sensitive cyclin D protein.

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 Astrocytes are necessary for blood-brain barrier maintenance in the adult mouse brain

2020 ◽  
Author(s):  
Benjamin P. Heithoff ◽  
Kijana K. George ◽  
Aubrey N. Phares ◽  
Ivan A. Zuidhoek ◽  
Carmen Munoz-Ballester ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Glucose Transporter ◽  
Morphological Changes ◽  
Cell Types ◽  
Adult Brain ◽  
Brain Barrier ◽  
Glucose Transporter 1 ◽  
Blood Brain ◽  
Junction Protein ◽  
The Brain

AbstractIn the adult brain, multiple cell types are known to produce factors that regulate blood-brain barrier properties, including astrocytes. Yet several recent studies disputed a role for mature astrocytes at the blood-brain barrier. To determine if astrocytes contribute a non-redundant and necessary function in maintaining the adult blood-brain barrier, we used a mouse model of tamoxifen-inducible astrocyte ablation. In adult mice, tamoxifen induction caused sparse apoptotic astrocyte cell death within 2 hours. Indicative of BBB damage, leakage of the small molecule Cadaverine and the large plasma protein fibrinogen into the brain parenchyma indicative of BBB damage was detected as early as astrocyte ablation was present. Vessels within and close to regions of astrocyte loss had lower expression of the tight junction protein zonula occludens-1 while endothelial glucose transporter 1 expression was undisturbed. Cadaverine leakage persisted for several weeks suggesting a lack of barrier repair. This is consistent with the finding that ablated astrocytes were not replaced. Adjacent astrocytes responded with partial non-proliferative astrogliosis, characterized by morphological changes and delayed phosphorylation of STAT3, which restricted dye leakage to the brain and vessel surface areas lacking coverage by astrocytes one month after ablation. In conclusion, astrocytes are necessary to maintain blood-brain barrier integrity in the adult brain. Blood-brain barrier-regulating factors secreted by other cell types, such as pericytes, are not sufficient to compensate for astrocyte loss.Main PointsMature astrocytes are necessary for maintenance of endothelial tight junctions in the adult brain. Ablated astrocytes are not replaced by proliferation or process extension of neighboring astrocytes resulting in long-term blood-brain barrier damage.

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