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)

Costameres, vinculin-containing structures found in skeletal and cardiac muscle, are thought to anchor the Z-discs of the peripheral myofibrils to the sarcolemma. Several lines of evidence indicate that two different sets of costameres, integrin- and N-cadherin-based, are present in cardiac muscles. In this study, immunoblot analysis was used to study the expression of N-cadherin, alpha-catenin, beta-catenin, vinculin, talin, and laminin in rat cardiac muscles at embryonic days 15 and 19, the day of birth (postnatal day 0), postnatal weeks 1, 2, 3, and 4, and in the adult. Double immunofluorescence microscopy was performed to study the spatial and temporal distribution of these two sets of costameres in rat cardiomyocytes. Costameric staining for N-cadherin, codistributed with beta-catenin, was strong from embryonic day 15 up to postnatal week 2, gradually decreased after postnatal week 3, and was undetectable at postnatal week 4 and in the adult. Confocal microscopy showed that N-cadherin colocalized with alpha-actinin at cortical myofibrils. Double-labeling of beta-catenin and talin indicated the coexistence of N-cadherin/catenin- and integrin/talin-based costameres in rat cardiac muscle. Although beta-catenin and vinculin were co-localized at the costamere of cardiomyocytes from embryonic day 15 to postnatal week 3, staining for beta-catenin or talin was mutually exclusive at all stages examined. These results demonstrate the simultaneous, but mutually exclusive, existence of N-cadherin/catenin- and integrin/talin-based costameres in rat cardiomyocytes between late embryonic stages and postnatal week 3, while only integrin/talin-based costameres were found in adult rats. The N-cadherin/catenin-based costameres in rat cardiac muscles may play a role in myofibrillogenesis similar to that of their counterparts in cultured cardiomyocytes.
 ...
PMID:Role of N-cadherin- and integrin-based costameres in the development of rat cardiomyocytes. 1183 97

The cytoplasmic face of cell contact sites comprises large macromolecular assemblies that link transmembrane cell adhesion molecules to the cytoskeleton. These assemblies are dynamic structures that are the targets of regulatory signals that control cell adhesiveness. Recent studies of the biochemistry and structure of the cadherin-catenin complex, vinculin and proteins of the ezrin/radixin/moesin family have begun to reveal the architecture of these assemblies and the mechanisms that are involved in their regulation.
 ...
PMID:The cytoplasmic face of cell contact sites. 1195 5

Abnormal expression of the alphaE-catenin protein, a component of the E-cadherin/catenin cell adhesion complex, is frequently observed in human cancer cells. An inverse correlation between alphaE-catenin expression and tumor malignancy can be of prognostic value. Mutations of the alphaE-catenin gene, CTNNA1, were described in several human cancer cell lines and were found to result in aberrant cell adhesion. We have developed a polymerase chain reaction/single-strand conformation polymorphism-based method for mutation analysis of this gene in human tumor DNA. This approach enabled us to identify several polymorphisms in a set of desmoid tumors, demonstrating that this method is suitable for alphaE-catenin mutational analysis. On the basis of our genomic characterization data, we found that the previously reported alternative splicing of the alphaE-catenin gene actually generates a frame-shift, resulting in a truncated alphaE-catenin protein. This finding is unlike the other alpha-catenin family members alphaN-catenin and vinculin, which show in-frame alternative inserts. Furthermore, real-time quantitative reverse transcriptase-PCR analysis did not reveal relevant expression levels of this alternatively spliced alphaE-catenin variant neither in any human tissue or cell line tested, nor at any mouse developmental stage tested. Thus, contrary to previous notions, alternative splicing with in-frame insertion nearby the C-terminal end of the protein is not a general feature for all members of the alpha-catenin/vinculin family.
 ...
PMID:The human alphaE-catenin gene CTNNA1: mutational analysis and rare occurrence of a truncated splice variant. 1199 91

The anucleate prismoid fiber cells of the eye lens are densely packed to form a tissue in which the plasma membranes and their associated cytoplasmic coat form a single giant cell-cell adhesive complex, the cortex adhaerens. Using biochemical and immunoprecipitation methods in various species (cow, pig, rat), in combination with immunolocalization microscopy, we have identified two different major kinds of cortical complex. In one, the transmembrane glycoproteins N-cadherin and cadherin-11 [which also occur in heterotypic ('mixed') complexes] are associated with alpha- and beta-catenin, plakoglobin (proportions variable among species), p120ctn and vinculin. The other complex contains ezrin, periplakin, periaxin and desmoyokin (and so is called the EPPD complex), usually together with moesin, spectrin(s) and plectin. In sections through lens fiber tissue, the short sides of the lens fiber hexagons appear to be enriched in the cadherin-based complexes, whereas the EPPD complexes also occur on the long sides. Moreover, high resolution double-label fluorescence microscopy has revealed, on the short sides, a finer, almost regular mosaicism of blocks comprising the cadherin-based, catenin-containing complexes, alternating with patches formed by the EPPD complexes. The latter, a new type of junctional plaque ensemble of proteins hitherto known only from certain other cell types, must be added to the list of major lens cortex proteins. We here discuss its possible functional importance for the maintenance of lens structure and functions, notably clear and sharp vision.
 ...
PMID:A novel cell-cell junction system: the cortex adhaerens mosaic of lens fiber cells. 1462 92

Intercellular adhesions are known to play an important role in differentiation of osteoblasts and in the development of bone tissue architecture. However, to our knowledge, they have never been studied during the formation of bone tissue in contact with a biomaterial surface. In an in vitro kinetic study, we followed the expression of proteins involved in cell-cell interactions (beta-catenin), in cell-material interactions (vinculin) and in cytoskeleton (actin) of human osteoblastic cells cultured on grooved titanium-based substrates during 1, 2, 4, 6, 24, 48, and 72 hours. The human osteoblasts aligned themselves in the 150 microm wide grooves only after 24 hours. The distribution of vinculin-positive focal contacts, actin cytoskeleton and beta-catenin positive-adherens junctions was not significantly influenced by the cell alignment. beta-catenin-positive adherens junctions were expressed by human osteoblasts as soon as 1 hour after inoculation. At this time, they showed a patch-like aspect along cytoplasmic processes in contact with an underlying or an adjacent cell. After 2 hours, the patches were more and more numerous underlining the connections between cells. After 4 hours and more, the patches were organised in a parallel arrangement perpendicular to the two connected cells forming a "zip-like" aspect. Additionally, using double immuno-staining, we demonstrated that sometimes beta-catenin and vinculin appeared co-localised and sometimes not. The linkage of catenin/cadherin complex and vinculin-positive focal contacts with actin filaments may explain this apparent co-localisation.
 ...
PMID:Kinetic study of the expression of beta-catenin, actin and vinculin during osteoblastic adhesion on grooved titanium substrates. 1547 1

Using a well characterized model of cell-cell actin-based adherens junction (AJ) disruption by suppressing the intratesticular testosterone level in adult rats with testosterone-estradiol implants, we have confirmed earlier findings that Sertoli-germ cell AJ dynamics are regulated by the activation of kinases via putative signaling pathways but with some unexpected findings as follows. First, the loss of germ cells from the seminiferous epithelium during androgen suppression was associated with a surge in myotubularin-related protein 2 (MTMR2, a lipid phosphatase, in which adult MTMR2-/- mice were recently shown to be azoospermic because of the loss of cell adhesion function between germ and Sertoli cells); kinases: phosphatidylinositol 3-kinase, c-Src, and C-terminal Src kinase; adaptors: alpha-actinin, vinculin, afadin, and p130 Crk-associated protein; and AJ-integral membrane proteins at the ectoplasmic specialization (ES, a testis-specific cell-cell actin-based AJ type) site: N-cadherin, beta-catenin, integrin beta1, and nectin 3. Second, MTMR2, instead of structurally interacting with phosphatidylinositol 3-kinase, a protein and lipid kinase, was shown to associate only with c-Src, a nonreceptor protein tyrosine kinase, as demonstrated by both coimmunoprecipitation and fluorescent microscopy at the site of apical ES, but none of the kinases, adaptors, and AJ-integral proteins that were examined. Collectively, these results suggest that the MTMR2/c-Src is an important phosphatase/kinase protein pair in AJ dynamics in the testis. Because c-Src is known to associate with the cadherin/catenin protein complex at the ES in the testis, we next sought to investigate any changes in the protein-protein interactions of this protein complex during androgen suppression-induced germ cell loss. Indeed, there was a loss of N-cadherin and beta-catenin association, accompanied by a surge in Tyr phosphorylation of beta-catenin, during germ cell loss from the epithelium. Third, and perhaps the most important of all, during natural recovery of the epithelium after removal of testosterone-estradiol implants when spermatids were reattaching to Sertoli cells, an increase in N-cadherin and beta-catenin association was detected with a concomitant loss in the increased Tyr phosphorylation in beta-catenin. In summary, these results illustrate that the cadherin/catenin is a crucial cell adhesion complex that regulates AJ dynamics in the testis, and its functionality is likely modulated by the MTMR2/c-Src protein complex.
 ...
PMID:Regulation of Sertoli-germ cell adherens junction dynamics via changes in protein-protein interactions of the N-cadherin-beta-catenin protein complex which are possibly mediated by c-Src and myotubularin-related protein 2: an in vivo study using an androgen suppression model. 1559 Nov 33

Alpha-catenin, a cadherin-associated protein, links cadherin/beta-catenin and cadherin/plakoglobin complexes to the actin cytoskeleton. This protein is required for the function of cadherins, cell adhesion molecules. We transfected an alpha-catenin-deficient colon carcinoma line, which cannot organize desmosomes, with a series of alpha-catenin mutant constructs. We examined the formation of desmosomes in these cells by immunofluorescence staining using anti-desmoglein and anti-desmoplakin antibodies. The results demonstrated that either the middle or the carboxy-terminal region of alpha-catenin was required for desmosome formation. Immunoblot analysis revealed that the amounts of desmoglein and desmoplakin did not differ significantly between cells that were capable of forming desmosomes and those that failed to form desmosomes. Cell surface biotinylation revealed that desmoglein was retained intracellularly in cells that could not organize desmosomes. The internal domain binds vinculin and alpha-actinin, actin-binding proteins, while the carboxy-terminal domain has the ability to bind and bundle actin filaments. These results indicate that the interaction of alpha-catenin and actin functions in the assembly of desmosomes in epithelial cells.
 ...
PMID:Identification of regions of alpha-catenin required for desmosome organization in epithelial cells. 1627 78

Spatial and functional organization of cells in tissues is determined by cell-cell adhesion, thought to be initiated through trans-interactions between extracellular domains of the cadherin family of adhesion proteins, and strengthened by linkage to the actin cytoskeleton. Prevailing dogma is that cadherins are linked to the actin cytoskeleton through beta-catenin and alpha-catenin, although the quaternary complex has never been demonstrated. We test this hypothesis and find that alpha-catenin does not interact with actin filaments and the E-cadherin-beta-catenin complex simultaneously, even in the presence of the actin binding proteins vinculin and alpha-actinin, either in solution or on isolated cadherin-containing membranes. Direct analysis in polarized cells shows that mobilities of E-cadherin, beta-catenin, and alpha-catenin are similar, regardless of the dynamic state of actin assembly, whereas actin and several actin binding proteins have higher mobilities. These results suggest that the linkage between the cadherin-catenin complex and actin filaments is more dynamic than previously appreciated.
 ...
PMID:Deconstructing the cadherin-catenin-actin complex. 1632 73

The adherens junction (AJ) densely associated with actin filaments is a major cell-cell adhesion structure. To understand the importance of actin filament association in AJ formation, we first analyzed punctate AJs in NRK fibroblasts where one actin cable binds to one AJ structure unit. The accumulation of AJ components such as the cadherin/catenin complex and vinculin, as well as the formation of AJ-associated actin cables depended on Rho activity. Inhibitors for the Rho target, ROCK, which regulates myosin II activity, and for myosin II ATPase prevented the accumulation of AJ components, indicating that myosin II activity is more directly involved than Rho activity. Depletion of myosin II by RNAi showed similar results. The inhibition of myosin II activity in polarized epithelial MTD-1A cells affected the accumulation of vinculin to circumferential AJ (zonula adherens). Furthermore, correct zonula occludens (tight junction) formation along the apicobasal axis that requires cadherin activity was also impaired. Although MDCK cells which are often used as typical epithelial cells do not have a typical zonula adherens, punctate AJs formed dependently on myosin II activity by inducing wound closure in a MDCK cell sheet. These findings suggest that tension generated by actomyosin is essential for correct AJ assembly.
 ...
PMID:Actomyosin tension is required for correct recruitment of adherens junction components and zonula occludens formation. 1651 85

Spermatogenesis is dependent on the ability of Sertoli cells to form mature junctions that maintain a unique environment within the seminiferous epithelium. Adjacent Sertoli cells form a junctional complex that includes classical adherens junctions and testis-specific ectoplasmic specialisations (ES). The regulation of inter-Sertoli cell junctions by the two main endocrine regulators of spermatogenesis, FSH and testosterone, is unclear. This study aimed to investigate the effects of FSH and testosterone on inter-Sertoli cell adherens junctions (as determined by immunolocalisation of cadherin, catenin and actin) and ES junctions (as determined by immunolocalisation of espin, actin and vinculin) in cultured immature Sertoli cells and GnRH-immunised adult rat testes given FSH or testosterone replacement in vivo. When hormones were absent in vitro, adherens junctions formed as discrete puncta between interdigitating, finger-like projections of Sertoli cells, but ES junctions were not present. The adherens junction puncta included actin filaments that were oriented perpendicularly to the Sertoli cell plasma membrane, but were not associated with the intermediate filament protein vimentin. When FSH was added in vitro, ES junctions formed, and adjacent adherens junction puncta fused into extensive adherens junction belts. After hormone suppression in vivo, ES junctions were absent, while FSH replacement restored ES junctions, as confirmed by electron microscopy and confocal analysis of ES-associated proteins. Testosterone alone did not affect adherens junctions or ES in vitro or in vivo. We conclude that FSH can regulate the formation of ES junctions and stimulate the organisation and orientation of extensive adherens junctions in Sertoli cells.
 ...
PMID:FSH regulates the formation of adherens junctions and ectoplasmic specialisations between rat Sertoli cells in vitro and in vivo. 1664 4


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