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

The cadherin/catenin complex mediates Ca2+-dependent cell-cell interactions that are essential for normal developmental processes. It has been proposed that sorting of cells during embryonic development is due, at least in part, to expression of different cadherin family members or to expression of differing levels of a single family member. Expression of dominant-negative cadherins has been used experimentally to decrease cell-cell interactions in whole organisms and in cultured cells. In this study, we elucidated the mechanism of action of extracellular domain-deleted dominant-negative cadherin, showing that it is not cadherin isotype-specific, and that it must be membrane-associated but the orientation within the membrane does not matter. In addition, membrane-targeted cytoplasmic domain cadherin with the catenin-binding domain deleted does not function as a dominant-negative cadherin. Expression of extracellular domain-deleted dominant-negative cadherin results in down-regulation of endogenous cadherins which presumably contributes to the non-adhesive phenotype.
 ...
PMID:Mechanism of extracellular domain-deleted dominant negative cadherins. 1021 55

The E-cadherin/catenin complex is a calcium-dependent cell-cell adhesion molecule, whose function is critical to the integrity of the adherens junction and which plays a role in the establishment and maintenance of normal epithelial morphology and differentiation. Loss of E-cadherin-mediated adhesion appears to be a fundamental aspect of the neoplastic phenotype which in some cases appears to be mediated by post-translational modifications (i.e. tyrosine phosphorylation) of its interacting proteins, the catenins which link E-cadherin to the actin cytoskeleton. There is increasing experimental evidence to suggest that epidermal growth factor receptor tyrosine phosphorylation may lead to the inactivation of the E-cadherin/catenin complex in cancer cells through its interaction with beta- or gamma-catenin in the cytoskeleton. Modulation of epidermal growth factor receptor activity by pharmacological agents has the potential to regulate a variety of cellular processes including adhesion, differentiation, and proliferation.
 ...
PMID:The E-cadherin/epidermal growth factor receptor interaction: a hypothesis of reciprocal and reversible control of intercellular adhesion and cell proliferation. 1036 89

Dysfunction of the cadherin-catenin complex, a key component of adherens junctions, is thought to confer invasive potential to cells. The aim of this study is to examine the expression and function of the E-cadherin/catenin complex in gastric carcinoma cell lines. Expression of E-cadherin, alpha, beta and gamma-catenin and p120ctn, and of the adenomatous polyposis coli protein (APC), together with function of the cadherin-catenin complex was examined in a panel of gastric carcinoma cell lines, using immunocytochemistry, Western blotting and a cell-cell aggregation assay. Protein interactions were examined by sequential immunoprecipitation and immunoblotting with antibodies to E-cadherin, alpha, beta and gamma-catenin, p120ctn and APC. Abnormalities of E-cadherin, alpha- and beta-catenin expression, were associated with disturbance of E-cadherin-catenin complex composition, loss of membranous localization and loss of calcium-dependent aggregation in six gastric carcinoma cell lines. APC protein expression and interaction with beta-catenin was preserved in five cell lines. We demonstrate frequent abnormalities of expression and function of E-cadherin and catenins, and associated disturbance of E-cadherin-mediated intercellular adhesion in gastric carcinoma cell lines. These findings support the tumour suppressor role of the E-cadherin and its contribution to the development and progression of the neoplastic phenotype in gastric carcinoma.
 ...
PMID:Abnormal expression and function of the E-cadherin-catenin complex in gastric carcinoma cell lines. 1040 33

E-cadherin, a calcium-dependent cell-cell adhesion molecule, is expressed in highly specific spatiotemporal patterns throughout metazoan development, notably at sites of embryonic induction. E-cadherin also plays a critical role in regulating cell motility/adhesion, cell proliferation, and apoptosis. We have used the continuously erupting rat incisor as a system for examining the expression of E-cadherin and the associated catenins [alpha-, beta-, gamma-catenin (plakoglobin) and p120(ctn)] during amelogenesis. Using immunhistochemical techniques, we observed expression of alpha-catenin and gamma-catenin in ameloblasts throughout amelogenesis. In contrast, expression of E-cadherin, beta-catenin, and p120(ctn) was strong in presecretory, transitional, and reduced stage ameloblasts (Stages I, III, and V) but was dramatically lower in secretory and maturation stage ameloblasts (Stages II and IV). This expression alternates with the expression pattern we previously reported for the adenomatous polyposis coli protein (APC), a tumor suppressor that competes with E-cadherin for binding to beta-catenin. We suggest that alternate expression of APC and the cadherin-catenin complex is critical for the alterations in cell-cell adhesion and other differentiated cellular characteristics, such as cytoskeletal alterations, that are required for the formation of enamel by ameloblasts.
 ...
PMID:The cadherin-catenin complex is expressed alternately with the adenomatous polyposis coli protein during rat incisor amelogenesis. 1068 93

1. The blood-brain barrier is essential for the maintenance and regulation of the neural microenvironment. The blood-brain barrier endothelial cells comprise an extremely low rate of transcytotic vesicles and a restrictive paracellular diffusion barrier. The latter is realized by the tight junctions between the endothelial cells of the brain microvasculature, which are subject of this review. Morphologically, blood-brain barrier-tight junctions are more similar to epithelial tight junctions than to endothelial tight junctions in peripheral blood vessels. 2. Although blood-brain barrier-tight junctions share many characteristics with epithelial tight junctions, there are also essential differences. However, in contrast to tight junctions in epithelial systems, structural and functional characteristics of tight junctions in endothelial cells are highly sensitive to ambient factors. 3. Many ubiquitous molecular constituents of tight junctions have been identified and characterized including claudins, occludin, ZO-1, ZO-2, ZO-3, cingulin, and 7H6. Signaling pathways involved in tight junction regulation comprise, among others, G-proteins, serine, threonine, and tyrosine kinases, extra- and intracellular calcium levels, cAMP levels, proteases, and TNF alpha. Common to most of these pathways is the modulation of cytoskeletal elements which may define blood-brain barrier characteristics. Additionally, cross-talk between components of the tight junction- and the cadherin-catenin system suggests a close functional interdependence of the two cell-cell contact systems. 4. Recent studies were able to elucidate crucial aspects of the molecular basis of tight junction regulation. An integration of new results into previous morphological work is the central intention of this review.
 ...
PMID:Tight junctions of the blood-brain barrier. 1069 May 2

Members of the cadherin family of cell adhesion molecules participate in calcium-dependent cell-cell adhesions that are necessary for the cell sorting events that regulate early developmental processes. Although individual cadherin molecules have been shown to participate in tissue histogenesis, the regulation of function of these receptors in cell differentiation has been more difficult to identify. We have determined that N-cadherin linkage to the cytoskeleton is correlated with lens cell differentiation in vivo. Through the use of a chick embryo lens culture system that mimics differentiation in vivo, we have determined that N-cadherin linkage to the cytoskeleton is altered and lens differentiation is blocked by function-blocking antibodies to N-cadherin. In the presence of the N-cadherin function-blocking antibody, NCD-2, both N-cadherin and filamentous actin are prevented from organizing at the cortical membranes. This correlates with an inhibition of lens morphogenesis and differentiation. These results are paralleled by changes in the expression of the molecular components of the cadherin-catenin complex and their linkage to the actin cytoskeleton. In the presence of NCD-2, expression of N-cadherin, alpha-catenin, and beta-catenin is inhibited and their association with the cytoskeleton blocked. Overall cadherin expression, however, remains unchanged as demonstrated by studies with a pan-cadherin antibody. This is accompanied by an increase in expression of the cadherin cytoskeletal protein plakoglobin. Although the cells have tried to compensate for the loss of N-cadherin by up-regulation of another cadherin(s) and plakoglobin, this is unable to compensate for N-cadherin function. The data strongly suggest that N-cadherin and its associated cytoskeleton play an important role in the differentiation process that leads to the formation of the crystalline lens.
 ...
PMID:N-cadherin function is required for differentiation-dependent cytoskeletal reorganization in lens cells in vitro. 1073 70

Ischemic epithelial cells are characterized by disruption of intercellular junctions and loss of apical-basolateral protein polarity, which are normally dependent on the integrity of the adherens junction (AJ). Biochemical analysis of both whole ischemic kidneys and ATP-depleted Madin-Darby canine kidney (MDCK) cells demonstrated a striking loss of E-cadherin (the transmembrane protein of the AJ) with the appearance and accumulation of an approximately 80-kDa fragment reactive with anti-E-cadherin antibodies on Western blots of ATP-depleted MDCK cells. This apparent ischemia-induced degradation of E-cadherin was not blocked by either inhibitors of the major proteolytic pathways (i.e., proteasome, lysosome, or calpain), or by chelation of intracellular calcium, suggesting the involvement of a protease capable of functioning at low ATP and low calcium levels. Immunocytochemistry revealed the movement of several proteins normally comprising the AJ, including E-cadherin and beta-catenin, away from lateral portions of the plasma membrane to intracellular sites. Moreover, rate-zonal centrifugation and immunoprecipitation with anti-E-cadherin and anti-beta-catenin antibodies indicated that ATP depletion disrupted normal E-cadherin-catenin interactions, resulting in the dissociation of alpha- and gamma-catenin from E-cadherin and beta-catenin-containing complexes. Because the generation and maintenance of polarized epithelial cells are dependent upon E-cadherin-mediated cell-cell adhesion and normal AJ function, we propose that the rapid degradation of E-cadherin and dissolution of the AJ is a key step in the development of the ischemic epithelial cell phenotype. Furthermore, we hypothesize that the reassembly of the AJ after ischemia/ATP depletion may require a novel bioassembly mechanism involving recombination of newly synthesized and sorted E-cadherin with preexisting pools of catenins that have (temporally) redistributed intracellularly.
 ...
PMID:Selective degradation of E-cadherin and dissolution of E-cadherin-catenin complexes in epithelial ischemia. 1080 98

Cadherins are calcium-dependent cell adhesion receptors with strong morphoregulatory functions. To mediate functional adhesion, cadherins must interact with actin cytoskeleton. Catenins are cytoplasmic proteins that mediate the interactions between cadherins and the cytoskeleton. In addition to their role in cell-cell adhesion, catenins also participate in signaling pathways that regulate cell growth and differentiation. Cadherins and catenins appear to be involved in melanocyte development and transformation. Here, we investigated the function of cadherin-catenin complexes in the normal development and transformation of melanocytes by studying the patterns of expression of the cell-cell adhesion molecules, E-, N- and P-cadherin, and the expression of their cytoplasmic partners, alpha-, beta- and gamma-catenin during murine development. Similar analyses were performed in vitro using murine melanoblast, melanocyte, and melanoma cell lines in the presence and absence of keratinocytes, the cells with which melanocytes interact in vivo. Overall, the results suggest that the expression of cadherins and catenins is very plastic and depends on their environment as well as the transformation status of the cells. This plasticity is important in fundamental cellular mechanisms associated with normal and pathological ontogenesis, as well as with tumorigenesis.
 ...
PMID:Plasticity of cadherin-catenin expression in the melanocyte lineage. 1095 94

Cadherins, calcium-dependent cell adhesion molecules, play crucial roles, not only in the maintenance of tissue integrity, but also in the regulation of many aspects of cell behavior. We investigated the expression of "classic" E-, N- and P-cadherins in bone marrow-derived cultured mast cells (BMMC) and peritoneal mast cells (PMC) from mice. Flow cytometric analysis and immunocytochemical staining indicated that E-cadherin was expressed on the cell surface of BMMC and also at lower levels on PMC. N-cadherin was also expressed on the surface of BMMC, but not of PMC, whereas P-cadherin expression was seen in neither cell type. Significant expression of E- and N-cadherin mRNA was observed in BMMC by reverse transcriptase-polymerase chain reaction (RT-PCR), but PMC expressed only E-cadherin mRNA. Western blotting analysis indicated expression of alpha- and beta-catenins and p120-catenin (or p120 cas) in BMMC, whereas PMC showed less intense expression of alpha- and beta-catenins with high levels of p120 expression. Analyses of beta-catenin or E-cadherin immunoprecipitates from BMMC lysate revealed that alpha-catenin, beta-catenin, and E-cadherin were co-precipitated, suggesting that E-cadherin and catenins form a complex in mast cells. Addition of a blocking antibody of homophilic E-cadherin interactions, or a synthetic E-cadherin-binding decapeptide containing the histidine-alanine-valine (HAV) sequence in methylcellulose cultures of gut intraepithelial mononuclear cells or BMMC, significantly suppressed the clonal growth of mast cells. Furthermore, the blocking antibody or synthetic decapeptide significantly suppressed BMMC adhesion to E-cadherin-expressing F9 cell monolayers. These results indicated that E-cadherin and associated cytoplasmic proteins in mast cells might be involved in the regulation of certain stages of mast cell differentiation and cell-cell interactions.
 ...
PMID:E-cadherin and cadherin-associated cytoplasmic proteins are expressed in murine mast cells. 1104 74

Arachnoid villi or granulations are small projections of the arachnoid barrier layer into the venous sinus and its major tributaries. They are closely related to the absorption of cerebrospinal fluid, and are widely accepted to be the origin of human meningiomas. Arachnoid villi and meningiomas show a number of similarities in ultrastructure, cell adhesion mechanisms, and extracellular matrix composition. Ultrastructurally, both arachnoid and meningioma cells are characterized by interdigitations connected with junctional complexes, and extracellular cisterns related to the fluid transport. Extracellular cisterns and the intercellular space reveal abundant membrane-derived multilamellar phospholipids when a conventional ultrastructural fixative supplemented with tannic acid is used. Both arachnoid and meningioma cells are connected by Ca2+-dependent adhesion molecules: epithelial-cadherins which are concentrated at the adherens junctions. Membrane-cytoskeleton interactions by means of merlin and a-catenin molecules are thought to be crucial in signal transduction resulting in contact inhibition of cell growth in normal arachnoid cells. Impairment of these molecules might be related to meningioma-genesis. Glutathione-independent prostaglandin D2 synthase [EC 5.3.99.2] responsible for the biosynthesis of prostaglandin D2 in the central nervous system is also consistently expressed in human arachnoid villi and meningiomas. The multilamellar phospholipids are conceivably related to this arachidonate metabolism.
 ...
PMID:On Arachnoid Villi and Meningiomas: Functional Implication of Ultrastructure, Cell Adhesion Mechanisms, and Extracellular Matrix Composition. 1117 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>