Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:B0FTZ7 (catenin)
 18,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cadherin/catenin complex is an essential regulator of intercellular adhesion and is critical for the establishment of epithelial cell polarity. The purpose of this study was to (1) determine the spatial pattern of cadherin and catenin expression, colocalization, and interaction along the mouse nephron, and (2) investigate the expression, localization, and interaction of proximal tubular cadherins and catenins during mercuric chloride-induced nephrotoxicity. Using a combination of Western blot analysis, colocalization studies, and coimmunoprecipitation, we conclude that two distinct cadherin/catenin complexes exist in adult mouse kidney proximal tubules: N-cadherin/beta-catenin/alpha-catenin and E-cadherin/beta-catenin/alpha-catenin/p120-catenin. In the distal tubule, E-cadherin/beta-catenin/alpha-catenin and E-cadherin/gamma-catenin/alpha-catenin complexes are present. Male C3H mice were challenged with 0-25 micromol/kg mercuric chloride i.p. (6-48 h) to assess the impact of nephrotoxicity on cadherin/catenin complexes. Plasma creatinine and blood urea nitrogen were increased between 6 and 48 h, indicating the onset of renal failure. In addition, histological evaluation demonstrated alterations in the proximal tubules. At 24 h, we observed decreases in Ksp- and N-cadherin, but not in E-cadherin. Additionally, alpha-catenin expression was decreased, in the absence of changes in beta-, gamma-, and p120-catenin. The early stages (6 h) of mercuric chloride-induced nephrotoxicity were associated with disruption of complex integrity. N-cadherin and alpha-catenin localizations were disrupted at 6 h. These changes in cadherin and catenin localization corresponded with a decrease in the coimmunoprecipitation of alpha-catenin with both beta-catenin and N-cadherin. Interestingly, these changes occurred at the same time that aberrant staining of Na+/K(+)-ATPase staining was seen. Taken together, these data suggest that alterations in cadherin and catenin expression, localization, and interaction are associated with nephrotoxicity.
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PMID:Disruption of cadherin/catenin expression, localization, and interactions during HgCl2-induced nephrotoxicity. 1508 54

The authors investigated the expression of N-cadherin and alphaN-catenin (which is strongly related to N-cadherin function) in the denervation/reinnervation process using a rat sciatic nerve and gastrocnemius model. In a rat model, the right sciatic nerve was exposed at the mid-thigh region, and the nerve was transected with small scissors. Then, the nerve was sutured using 10-0 monofilament perineurial nylon sutures. At various periods up to 24 weeks after the operation, the gastrocnemius muscle of the treated hindlimbs was removed. Four rats were used at each time point in both groups. N-cadherin and alphaN-catenin expressions were detected by Western blot analysis and immunofluorescent staining with anti N-cadherin and alphaN-catenin antibodies. The level of N-cadherin was already elevated in the first postoperative week, and the level in the second postoperative week was almost the same as in the first. The level decreased gradually after the fourth postoperative week and, in the ninth postoperative week, returned to almost the same as the control level. The level of alphaN-catenin was almost the same as the control (1.0) within the second postoperative week. After the fourth postoperative week, the level elevated gradually, with a peak in the sixth postoperative week. The level then decreased and returned almost to that of the control after the twelfth postoperative week. Immunofluorescent staining was observed along the muscular membrane in all specimens of both proteins, and the time course of the degree of immunofluorescent staining was similar to the results of Western blot analysis. These results suggest that N-cadherin and alphaN-catenin expressions are elevated in the degeneration/regeneration processes of the muscle after nerve injury, but that the kinetics between the two proteins differ.
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PMID:Expression of N-cadherin and alphaN-catenin in the degeneration/regeneration process of rat skeletal muscle after nerve injury. 1508 12

E-cadherin functions as suppressor of invasion in epithelial cells and its loss is described in many invasive carcinomas. In some tumours, the disappearance of E-cadherin has been correlated with upregulation of other classical cadherins, such as N- or P-cadherin. To analyse the different cellular functions of cadherin molecules, we stably expressed E-cadherin or N-cadherin in the E- and N-cadherin-deficient pancreatic tumour cell line MIA PaCa-2. Only E-cadherin was able to induce a mesenchymal-epithelial transition and suppressed invasion of MIA PaCa-2 cells. Furthermore, only re-expression of E-cadherin resulted in an upregulation of alpha- and beta-catenin mRNAs and protein concentrations. Ectopically expressed N-cadherin failed to assemble cadherin/catenin adhesion complexes and failed to inhibit invasion. Analysis of p120(ctn), which was associated with both cadherins, demonstrated that E-cadherin was linked to a shorter isoform of p120(ctn). In contrast, N-cadherin was associated with the long, 120 kDa p120(ctn) isoforms. In addition, p120(ctn) connected with N-cadherin was phosphorylated at tyrosine residues, whereas the isoform linked to E-cadherin was not phosphorylated. Thus, the differences between E- and N-cadherin in recruiting different phosphorylated isoforms of p120(ctn) to the membrane might be responsible for the inability of N-cadherin to replace E-cadherin as suppressor of invasion in pancreatic carcinoma cells.
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PMID:E- and N-cadherin differ with respect to their associated p120ctn isoforms and their ability to suppress invasive growth in pancreatic cancer cells. 1510 17

Aging is associated with a loss of renal reserve, and increased sensitivity to either xenobiotic or physiologic insult. Given the critical role of the cadherin/catenin complex in establishing and maintaining the integrity and polarity of tubular epithelial cells, it was hypothesized that aging was associated with alterations in renal cadherin/catenin complexes. Histological assessment of aged (24 months) kidneys harvested from male Fischer 344 rats demonstrates mild degeneration of proximal tubules, multifocal chronic lymphocytic infiltration, moderate development of protein casts inside tubules, and tubular dilatation or degeneration. Western blot analysis revealed that N-cadherin protein expression is not constant over 24 months. N-cadherin expression increased from 4 to 9 months, with peak levels at 9 and 13 months. A decrease in expression was seen at 19 months and an almost complete loss of expression was seen at 24 months. In contrast, the expression of E- and Ksp-cadherin was constant over 24 months. A loss of alpha-catenin at was seen at 19 and 24 months in the absence of changes in beta-, gamma-, and p120-catenin. This pattern of N-cadherin expression (increase followed by decrease) was confirmed by real-time PCR analysis, which demonstrated a similar pattern as the Western blot, suggesting that the loss of N-cadherin protein was due to decreased gene expression. The loss of N-cadherin was specific for the kidney, as no changes in N-cadherin expression in the liver, brain, or testes were seen during aging. The conclusion that loss of N-cadherin expression is a critical component of the renal dysfunction associated with aging is supported by the finding that caloric restriction attenuates the loss of N-cadherin, as well as the finding that a significant loss of N-cadherin is seen in the kidneys of ZDF x SHHF rats, a genetic model of end-stage renal disease. Cadherin and catenin expression was further analyzed by immunofluorescence. A significant loss of staining of both N-cadherin and alpha-catenin was seen in the proximal tubules of rats at 24 months. Interestingly, this corresponded with delocalization of the alpha-1 subunit of the Na+K+-ATPase, i.e. aberrant staining on cell-cell borders and some indication of apical staining in proximal tubules. Taken together, these data suggest that aging is associated with decreased expression of N-cadherin and alpha-catenin and is associated with a loss of cell polarity.
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PMID:Loss of N-cadherin and alpha-catenin in the proximal tubules of aging male Fischer 344 rats. 1517 34

N-cadherin is expressed throughout skeletal myogenesis and has been proposed to be involved in the differentiation program of myogenic precursors. Here, we further characterize the N-cadherin involvement and its mechanism of action at the onset of differentiation, through controlled N-cadherin activation by plating isolated C2 myoblasts on surfaces coated with a chimeric Ncad-Fc homophilic ligand (N-cadherin ectodomain fused to the immunoglobulin G Fc fragment). We show that N-cadherin activation substitutes for the cell density in myogenic differentiation by promoting myogenin and troponin T expression. In addition, N-cadherin adhesion participates to the associated cell cycle arrest through the nuclear accumulation of cyclin-dependent kinase inhibitors p21 and p27. Mouse primary myoblast cultures exhibited similar responses to N-cadherin as C2 cells. RNA interference knockdowns of the N-cadherin-associated cytoplasmic proteins p120 and beta-catenin produced opposite effects on the differentiation pathway. p120 silencing resulted in a decreased myogenic differentiation, associated with a reduction in cadherin-catenin content, which may explain its action on myogenic differentiation. beta-Catenin silencing led to a stimulatory effect on myogenin expression, without any effect on cell cycle. Our results demonstrate that N-cadherin adhesion may account for cell-cell contact-dependent cell cycle arrest and differentiation of myogenic cells, involving regulation through p120 and beta-catenins.
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PMID:N-cadherin activation substitutes for the cell contact control in cell cycle arrest and myogenic differentiation: involvement of p120 and beta-catenin. 1519 93

Cadherins and their associated cytoplasmic proteins, catenins, are critical to the maintenance of normal tissue integrity and the suppression of cancer invasion. The cadherin profile in malignant mesothelioma (MM) is not well defined and the role of the cadherin-catenin system in the pathogenesis of MM remains to be determined. By means of Western blot analysis and immunohistochemistry the expression of E (epithelial)-, N (neural)-, P (placental)-cadherin, and alpha-, beta- and gamma-catenins was studied in nine human MM cell lines and five human mesothelial cell lines. Mesothelial cells consistently expressed only N-cadherin and alpha- and beta-catenins. All but one MM cell line were N-cadherin-positive and all of them were also positive for alpha- and beta-catenins. E-cadherin was found in six (66.7%) and gamma-catenin in seven (77.8%) MM cell lines. Five of these E-cadherin-positive lines co-expressed N-cadherin and the remaining one was also P-cadherin-positive. Double immunofluorescence staining revealed the plasma membrane co-localisation of both cadherin types in MM cell lines that co-expressed E- and N-cadherin or E- and P-cadherin, respectively. Immunoprecipitation showed complexes of beta-catenin with both cadherin types when co-expressed. The results point to upregulation of E-cadherin and gamma-catenin in most MM cases and demonstrate that cadherin expression is more heterogeneous and less mutually exclusive in MM compared with the mesothelium, although the biological significance of this finding remains unclear.
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PMID:Aberrant E-cadherin and gamma-catenin expression in malignant mesothelioma and its diagnostic and biological relevance. 1526 32

Vascular stabilization, a process by which nascent vessels are invested with mural cells, is important in angiogenesis. Here we describe the molecular basis of vascular stabilization regulated by sphingosine 1-phosphate (S1P), a platelet-derived lipid mediator. S1P1 receptor-dependent cell-surface trafficking and activation of the cell-cell adhesion molecule N-cadherin is essential for interactions between endothelial and mural cells. Endothelial cell S1P1/Gi/Rac pathway induces microtubule polymerization, resulting in trafficking of N-cadherin to polarized plasma membrane domains. S1P treatment modulated the phosphorylation of N-cadherin as well as p120-catenin and induced the formation of cadherin/catenin/actin complexes containing novel regulatory and trafficking factors. The net result of endothelial cell S1P1 receptor activation is the proper trafficking and strengthening of N-cadherin-dependent cell-cell adhesion with mural cells. Perturbation of N-cadherin expression with small interfering RNA profoundly attenuated vascular stabilization in vitro and in vivo. S1P-induced trafficking and activation of N-cadherin provides a novel mechanism for the stabilization of nascent blood vessels by mural cells and may be exploited to control angiogenesis and vascular diseases.
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PMID:Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization. 1537 28

Delta-catenin (delta-catenin) is a neuron-specific catenin, which has been implicated in adhesion and dendritic branching. Moreover, deletions of delta-catenin correlate with the severity of mental retardation in Cri-du-Chat syndrome (CDCS), which may account for 1% of all mentally retarded individuals. Interestingly, delta-catenin was first identified through its interaction with Presenilin-1 (PS1), the molecule most frequently mutated in familial Alzheimer's Disease (FAD). We investigated whether deletion of delta-catenin would be sufficient to cause cognitive dysfunction by generating mice with a targeted mutation of the delta-catenin gene (delta-cat(-/-)). We observed that delta-cat(-/-) animals are viable and have severe impairments in cognitive function. Furthermore, mutant mice display a range of abnormalities in hippocampal short-term and long-term synaptic plasticity. Also, N-cadherin and PSD-95, two proteins that interact with delta-catenin, are significantly reduced in mutant mice. These deficits are severe but specific because delta-cat(-/-) mice display a variety of normal behaviors, exhibit normal baseline synaptic transmission, and have normal levels of the synaptic adherens proteins E-cadherin and beta-catenin. These data reveal a critical role for delta-catenin in brain function and may have important implications for understanding mental retardation syndromes such as Cri-du-Chat and neurodegenerative disorders, such as Alzheimer's disease, that are characterized by cognitive decline.
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PMID:Deletion of the neuron-specific protein delta-catenin leads to severe cognitive and synaptic dysfunction. 1538 68

Earlier studies in multiple epithelia have shown that cell-cell actin-based adherens junction (AJ) dynamics are regulated, at least in part, by the interplay of kinases and phosphatases that determines the intracellular phosphoprotein content. Yet it is virtually unknown regarding the role of protein kinases in Sertoli-germ cell AJ dynamics in the seminiferous epithelium of the testis. To address this issue, an in vitro coculture system utilizing Sertoli and germ cells was used to study the regulation of several protein kinases, including c-Src (the cellular form of the v-src transforming gene of Rous Sarcoma virus, RSV), carboxyl-terminal Src kinase (Csk), and casein kinase 2 (CK2), during AJ assembly. Both Sertoli and germ cells were shown to express c-Src, Csk, and CK2 with a relative Sertoli:germ cell ratio of approximately 1:1, suggesting both cell types contributed equally to the pool of these kinases in the epithelium. c-Src and Csk were shown to be stage-specific proteins during the epithelial cycle, being highest at stages VII-VIII. Studies using immunoprecipitation have illustrated that these kinases were structurally associated with the N-cadherin/beta-catenin, but not the nectin/afadin, protein complex, implicating that the cadherin/catenin protein complex is their likely putative substrate. An induction in c-Src, Csk, and CK2 were detected during Sertoli-germ cell AJ assembly in vitro but not when Sertoli cells were cultured alone. When adult rats were treated with 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide (AF-2364), a compound known to induce germ cell loss from the seminiferous epithelium, in particular elongating/elongate and round spermatids, by disrupting Sertoli-germ cell AJs, an induction of c-Src and Csk, but not CK2, was detected. Furthermore, a transient increase in the intrinsic kinase activities of c-Src, but not CK2, was also detected. This event was also associated with a loss of protein-protein association of N-cadherin and beta-catenin from the cadherin/catenin/c-Src/Csk/CK2 protein complex. Administration of PP1, a c-Src inhibitor, into adult rats via the jugular vein could induce the loss of spermatocytes and round spermatids, but not elongating/elongate spermatids, from the seminiferous epithelium. This result thus implicates the importance of c-Src in maintaining the integrity of AJs and possibly desmosome-like junctions between Sertoli cells and spermatocytes/round spermatids. In short, the data reported herein have shown that c-Src, Csk, and CK2 are novel protein kinases in AJ dynamics in the testis.
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PMID:Protein kinases and adherens junction dynamics in the seminiferous epithelium of the rat testis. 1538 20

The cadherin/catenin complex is a major transmembrane signaling complex through which extracellular signals can influence the cytoskeleton. It is present in neuronal processes during early development (J. Neurosci. 18 (1998) 6892) and appears to play multiple roles during neural circuit formation and maturation (Nat. Neurosci. 7 (2004) 357; Neuron 35 (2002) 77; Nat. Neurosci. 6 (2003) 1169). In previous work (Nat. Neurosci. 6 (2003) 1169), we showed that molecular manipulation of the cadherin/catenin complex has significant effects on the dendritic aborization of cultured hippocampal neurons at 9 days in vitro (d.i.v.). Here we extend these observations by examining the effects of over-expression of beta-catenin (fused to GFP; GFP-beta-cat(*)) or sequestering endogenous beta-catenin [using the intracellular domain of N-cadherin; Ncad(intra)] in cultured hippocampal neurons at different developmental stages. When transfected at 1 d.i.v. and assayed 48 h later, over-expression of GFP-beta-cat(*) increased axonal length and complexity, while sequestering endogenous beta-catenin had the opposite effect. Dendritic aborization was also enhanced by GFP-beta-cat(*) expression throughout early development although the magnitude of this effect decreased as neurons matured from 3 to 12 d.i.v. Finally, at 12 d.i.v., GFP-beta-cat(*) expression increased the density of dendritic spines although not the relative proportion of different subtypes of spines. These results demonstrate that the cadherin/catenin complex plays multiple roles in the development of neuronal morphology and that these roles change as neurons mature.
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PMID:Multiple functions for the cadherin/catenin complex during neuronal development. 1545 49


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