α-Catenin Is a Molecular Switch that Binds E-Cadherin-β-Catenin and Regulates Actin-Filament Assembly

Drees, Frauke; Pokutta, Sabine; Yamada, Sōichiro; Nelson, W. James; Weis, William I.

doi:10.1016/j.cell.2005.09.021

Cited by 898 publications

(893 citation statements)

References 56 publications

(85 reference statements)

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“…b-catenin, p120 and VE-cadherin form a complex. Formation of this ternary complex stabilizes the adherens junction 38 . Distance of adherens junction is at least 22.5 nm.…”

Section: Methodsmentioning

confidence: 99%

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

et al. 2013

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The use of nanomaterials has raised safety concerns, as their small size facilitates accumulation in and interaction with biological tissues. Here we show that exposure of endothelial cells to TiO 2 nanomaterials causes endothelial cell leakiness. This effect is caused by the physical interaction between TiO 2 nanomaterials and endothelial cells' adherens junction protein VE-cadherin. As a result, VE-cadherin is phosphorylated at intracellular residues (Y658 and Y731), and the interaction between VE-cadherin and p120 as well as b-catenin is lost. The resulting signalling cascade promotes actin remodelling, as well as internalization and degradation of VE-cadherin. We show that injections of TiO 2 nanomaterials cause leakiness of subcutaneous blood vessels in mice and, in a melanoma-lung metastasis mouse model, increase the number of pulmonary metastases. Our findings uncover a novel non-receptor-mediated mechanism by which nanomaterials trigger intracellular signalling cascades via specific interaction with VE-cadherin, resulting in nanomaterial-induced endothelial cell leakiness.

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“…b-catenin, p120 and VE-cadherin form a complex. Formation of this ternary complex stabilizes the adherens junction 38 . Distance of adherens junction is at least 22.5 nm.…”

Section: Methodsmentioning

confidence: 99%

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

et al. 2013

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“…[4][5][6] Recent studies have revealed the surprising fact that cadherins are necessary for the early recognition of neighboring cells during mesenchymalepithelial transition, whereas a-catenin and the actin cytoskeleton are more important in the maintenance of an epithelial phenotype. [7][8][9] On the basis of these observations it is obvious that linkages between the components of adherens junctions (AJ), a-catenin, b-catenin, p120catenin, a-actinin and vinculin, are targets of complex signalling mechanisms regulated by Rho family GTPases, and various kinases and phosphatases. 10 In addition to cell-cell contacts, integrinmediated cell-ECM contacts are crucial for the differentiation of epithelial cells.…”

mentioning

confidence: 99%

Different responses in transformation of MDCK cells in 2D and 3D culture by v-Src as revealed by microarray techniques, RT-PCR and functional assays

Töyli

Rosberg-Kulha

Capra

et al. 2010

Laboratory Investigation

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Differentiation and transformation of untransformed and ts-Src-transformed canine kidney MDCK cells in 2D and 3D environment were investigated using microarray technique, RT-PCR, confocal microscopy and functional assays. Activated Src induced epithelial-mesenchymal transition (EMT) in 2D environment followed by translocation of junctional proteins to the cytoplasm, without significant changes in protein expression. In 3D environment untransformed MDCK cells formed cell cysts with apical domain facing a lumen, E-cadherin delineating the lateral membranes, ZO-1 at tight junctions and caspase-3 in apoptotic cells captured within the lumen. This was accompanied by reduced expression of an apoptosis inhibitor, survivin and vesicle transport effectors, rab 7 and 8, whereas rab 5 expression increased. In 3D environment activated Src induced changes in expression of over 100 genes as revealed by microarray analysis, mostly involved in cell signaling, division and energy metabolism. Only response in cytoskeletal components was decreased expression of actin and Arp2/3 by v-Src, whereas two p120catenin binding proteins Kaiso and Nanos increased their expression. Concomitantly, apoptosis was inhibited by v-Src resulting in formation of a sphere with epitheloid cells facing extracellular matrix and undifferentiated cells captured within the cluster. This was accompanied by increased expression of apoptosis inhibitor survivin, as revealed by western blotting. Mitochondrial membrane potential in untransformed MDCK cells was lower than in ts-Src-MDCK cells in early days of cluster formation correlating with the induction of apoptosis. Hence, v-Src activation in 3D environment did not induce EMT, but brought about inhibition of apoptosis and increased proliferation where increased expression of survivin and inhibition of the mitochondrial permeability have a role.

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“…Interestingly, we observed changes in the genes underlying cytoskeletal architecture; namely dynein complex, ephrin b, cadherin, and integrin genes were more highly expressed in dyskinetic rats compared to both untreated parkinsonian controls and non-dyskinetic animals. Cadherins and catenins, along with Arc, are known to interact with and alter the actin cytoskeleton structure (Tanaka et al, 2000;Drees et al, 2005); Figure 5). We propose that this increase in transcription may indicate a mechanism for the previously observed increase in the number of synapses in dyskinetic animals (Zhang et al, 2013;Fieblinger et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Striatal mRNA expression patterns underlying peak dose l-DOPA-induced dyskinesia in the 6-OHDA hemiparkinsonian rat

et al. 2016

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L-DOPA is the primary pharmacological treatment for relief of the motor symptoms of ParkinsonÕs disease. With prolonged treatment (≥5 years) the majority of patients will develop abnormal involuntary movements as a result of L-DOPA treatment, known as L-DOPA-induced dyskinesia. Understanding the underlying mechanisms of dyskinesia is a crucial step towards developing treatments for this debilitating side effect. We used the 6-OHDA rat model of ParkinsonÕs disease treated with a three week dosing regimen of L-DOPA plus the dopa decarboxylase inhibitor benserazide (4 mg/kg and 7.5 mg/kg s.c., respectively) to induce dyskinesia in 50% of individuals. We then used RNA-seq to investigate the differences in mRNA expression in the striatum of dyskinetic animals, nondyskinetic animals, and untreated parkinsonian controls at the peak of dyskinesia expression, 60 minutes after L-DOPA administration. Overall, 255 genes were differentially expressed; with significant differences in mRNA expression observed between all three groups. In dyskinetic animals 129 genes were more highly expressed and 14 less highly expressed when compared with non-dyskinetic and untreated parkinsonian controls. In L-DOPA treated animals 42 genes were more highly expressed and 95 less highly expressed when compared with untreated parkinsonian controls. Gene set cluster analysis revealed an increase in expression of genes associated with the cytoskeleton and phosphoproteins in dyskinetic animals compared with non-dyskinetic animals, which is consistent with recent studies documenting an increase in synapses in dyskinetic animals. These genes may be potential targets for drugs to ameliorate L-DOPA-induced dyskinesia or as an adjunct treatment to prevent their occurrence. ¥ Cytoskeletal elements present a potential target for treatments to prevent or ameliorate L-DOPA-induced dyskinesia.

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α-Catenin Is a Molecular Switch that Binds E-Cadherin-β-Catenin and Regulates Actin-Filament Assembly

Cited by 898 publications

References 56 publications

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

Different responses in transformation of MDCK cells in 2D and 3D culture by v-Src as revealed by microarray techniques, RT-PCR and functional assays

Striatal mRNA expression patterns underlying peak dose l-DOPA-induced dyskinesia in the 6-OHDA hemiparkinsonian rat

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