Molecular organization of the uvomorulin-catenin complex.

Ozawa, Masayuki; Kemler, Rolf

doi:10.1083/jcb.116.4.989

Cited by 352 publications

(239 citation statements)

References 26 publications

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“…These data are in excellent agreement with the results presented in Figure 5. Ozawa and Kemler, 1992; briefly reviewed by Takiechi, 1991). While the cytoskeletal network of mammalian Sertoli cells has been well-described and is known to consist in part of extensive and localized bundles of actin filaments closely apposed to both tight junctions and another form of cell-cell adhesion, the ectoplasmic specialization (Vogl et al, 1986), the expression of catenins in Sertoli cells remains unexplored.…”

Section: Discussionmentioning

confidence: 99%

N‐cadherin mediates sertoli cell‐spermatogenic cell adhesion

Newton

Blaschuk

Millette

1993

Developmental Dynamics

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The complex topological association of Sertoli cells and spermatogenic cells in the testis suggests the existence of cell surface adhesion molecules that regulate cellular interactions within the seminiferous epithelium. The recent report of N-cadherin mRNA expression in the mouse testis implies the involvement of this known adhesion molecule in testicular cell binding. Accordingly, here we report that (1) N-cadherin is found on the surface membranes of rat spermatogenic cells and on Sertoli cells, and (2) that N-cadherin is a partial mediator of Sertoli cell-germ cell adhesion as tested in an in vitro cellcell binding assay. Antiserum directed against the N-cadherin cell adhesion recognition sequence was used for Western blot analysis of purified plasma membranes from Sertoli cells and from spermatogenic cells. Both membrane preparations exhibited reactivity at an appropriate M, of about 130 kDa. In addition, immunofluorescence assays demonstrated that both germ cells and Sertoli cells were labeled by anti-N-cadherin. Finally, the antiserum was included in a cytometer-assisted cell-cell binding test to determine its inhibitory ability. The antiserum consistently reduced specific testicular cell-cell adhesion by 30%-50%. This is the first demonstration that antibodies directed against the cadherin cell adhesion recognition sequence are capable of inhibiting cell-cell interactions. Pre-incubation of either rat Sertoli cells or spermatogenic cells alone was sufficient to achieve statistically significant inhibition of intercellular adhesion. We conclude, therefore, that N-cadherin is expressed by both Sertoli cells and spermatogenic cells and that N-cadherin is one of a number of regulatory molecules mediating local cellular associations in the mammalian seminiferous tubule. o 1993 Wiley-Liss, Inc.

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Section: Discussionmentioning

confidence: 99%

N‐cadherin mediates sertoli cell‐spermatogenic cell adhesion

Newton

Blaschuk

Millette

1993

Developmental Dynamics

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“…1). Interactions between epithelial cells are stabilized by linkage of cadherin-catenin complexes to the cortical actin network in adherens junctions (Ozawa and Kemler, 1992), and transient or permanent inactivation of adherens junction complexes is required for cell migration/ invasion (Birchmeier and Behrens, 1994;Takeichi, 1993). The establishment of a cortical actin filament network is necessary for localization of cadherincatenin complexes at adherens junctions in epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggested that cadherin proteins synthesized in 3D2.26 cells were unstable and proteolytically degraded. On the other hand, the levels of ␤-catenin, a cytoplasmic protein that links cadherin receptors to the actin cytoskeleton through its interaction with ␣-catenin in adherens junctions (Ozawa and Kemler, 1992), were unchanged in the transfectants (Fig. 3B), and ␤-catenin served as an internal protein loading marker.…”

Section: Scholl Et Almentioning

confidence: 99%

Ectopic Expression of PA2.26 Antigen in Epidermal Keratinocytes Leads to Destabilization of Adherens Junctions and Malignant Progression

Scholl

Gamallo

Quintanilla

2000

Laboratory Investigation

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SUMMARY: PA2.26 antigen is a small mucin-type transmembrane glycoprotein induced in mouse epidermal keratinocytes during carcinogenesis. It is located at plasma membrane projections, such as microvilli and ruffles, where it interacts with the actin cytoskeleton. Previous studies revealed that ectopic expression of PA2.26 in epidermal MCA3D keratinocytes induces cell surface extensions and increased motility. Here, we show that PA2.26-expressing MCA3D (3D2.26) cell transfectants undergo a phenotypic conversion linked to the acquisition of malignant characteristics. The 3D2.26 cells down-regulate basal keratin K14 and up-regulate vimentin and keratin K8 expression. Immunofluorescence analysis in 3D2.26 cell cultures showed loss of cortical actin filaments and destabilization of adherens junctions mediated by E-and P-cadherin, although both cadherin mRNAs were expressed in the transfectants. When the cadherin protein levels were analyzed in Western blots, no P-cadherin protein or smaller polypeptide E-cadherin forms were detected, suggesting that E-and P-cadherin synthesized in 3D2.26 cells was unstable and proteolytically degraded. Transplantation of 3D2.26 cells into athymic nude mice induced tumors, whereas MCA3D cells and control (3DN) transfectants were not tumorigenic after 72 days postinjection. The phenotype of the tumors was undifferentiated, with mixed regions exhibiting a glandular differentiation pattern in which the presence of numerous surface microvilli was observed at the ultrastructural level. Interestingly, PA2.26 antigen was highly expressed in these microvillous cell surfaces. Tumor cells were vimentin-and K8-positive and showed an aberrant pattern of E-cadherin protein expression in which large cytoplasmic aggregates were found close to the nucleus. Infiltration of tumor cells into lymphatic vessels and the presence of frequent regional lymph node metastases were also observed in the tumors. These results indicate that expression of PA2.26 antigen in premalignant keratinocytes induces a fully transformed and metastatic phenotype, and they suggest an involvement of PA2.26 in malignant progression. (Lab Invest 2000, 80:1749 -1759. P A2.26 antigen was identified as a cell-surface protein of about 45 kDa induced in basal-like keratinocytes and dermal fibroblasts during mouse epidermal carcinogenesis and skin remodeling processes. PA2.26 is absent from cultured nontumorigenic keratinocytes, but it is expressed in carcinoma cell lines and cultured active fibroblasts (Gandarillas et al, 1997). The molecular and biochemical characterization of PA2.26 revealed that it is a small mucin-like transmembrane sialoglycoprotein of 172 amino acids, located at microvilli, filopodia, lamellipodia, and ruffles. In normal tissues, PA2.26 is expressed in different type of cells: in the epithelia of choroid plexuses, ependyma, glomeruli, and alveoli, in all mesothelia, and in endothelia of lymphatic vessels, always concentrated at the apical plasma membranes and microvillous projections (Scholl et al, 1999).OTS-8 an...

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“…E-cadherin binds ␤-catenin in a 1:1 stoichiometric complex (Ozawa and Kemler, 1992;Huber and Weis, 2001). Therefore, one explanation for ␤-catenin stability and for its continued peripheral localization in E-cadherin depleted cells is that E-cadherin exists in large excess over ␤-catenin, and the reduction in E-cadherin by RNAi would then be insufficient to disrupt the complex.…”

Section: E-cadherin-␤-catenin Complex Is Disrupted In E-cadherin Knocmentioning

confidence: 99%

Depletion of E-Cadherin Disrupts Establishment but Not Maintenance of Cell Junctions in Madin-Darby Canine Kidney Epithelial Cells

Capaldo

Macara

2007

MBoC

238

206

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E-cadherin forms calcium-dependent homophilic intercellular adhesions between epithelial cells. These contacts regulate multiple aspects of cell behavior, including the organization of intercellular tight junctions (TJs). To distinguish between the roles of E-cadherin in formation versus maintenance of junctions, Madin-Darby canine kidney (MDCK) cells were depleted of E-cadherin by RNA interference. Surprisingly, reducing E-cadherin expression had little effect on the protein levels or localization of adherens junction (AJ) or TJ markers. The cells underwent morphological changes, as the normally flat apical surface swelled into a dome. However, apical-basal polarity was not compromised, transmembrane resistance was normal, and zonula occludin protein 1 dynamics at the TJs were unchanged. Additionally, an E-cadherin/ Cadherin-6 double knockdown also failed to disrupt established TJs, although ␤-catenin was lost from the cell cortex. Nevertheless, cells depleted of E-cadherin failed to properly reestablish cell polarity after junction disassembly. Recovery of cell-cell adhesion, transepithelial resistance, and the localization of TJ and AJ markers were all delayed. In contrast, depletion of ␣-catenin caused long-term disruption of junctions. These results indicate that E-cadherin and Cadherin-6 function as a scaffold for the construction of polarized structures, and they become largely dispensable in mature junctions, whereas ␣-catenin is essential for the maintenance of functional junctions. INTRODUCTIONThe cadherins are a large family of transmembrane glycoproteins that form homophilic, calcium-dependent interactions with neighboring cells (Takeichi, 1988;Gumbiner, 2000;Nollet et al., 2000). Cadherin family members include type I cadherins (E-, N-, P-, and R-cadherin), type II cadherins (Cadherin-6 and VE-cadherin), desmosomal cadherins (desmocollins and desmogleins), and a large subfamily of cadherin-like molecules (Nollet et al., 2000). The predominant epithelial isoform, E-cadherin, localizes to the lateral membrane of differentiated epithelia, providing the structural foundation for adherens junctions (AJs), a multiprotein complex that links cell-cell contacts to the actin cytoskeleton and various signaling molecules (PerezMoreno et al., 2003). The extracellular domain is composed of five ectodomain modules (ECs), with the most membranedistal module (EC1) mediating binding with the E-cadherin on the adjacent cell (Boggon et al., 2002). Calcium ions bind between the EC domains to promote a rod-like conformation required for transinteractions (Gumbiner, 1996;Patel et al., 2006). The cytoplasmic tail of E-cadherin binds to the armadillo repeat protein ␤-catenin, an important target of the Wnt signaling pathway and a cofactor for TCF/LEF-mediated transcription (Gavard and Mege, 2005). The ␤-catenin in turn binds ␣-catenin, which interacts with actin, as well as several actin-binding proteins: vinculin, formins, ␣-actinin, zonula occludin protein (ZO)-1, and afadin (Bershadsky, 2004). Cell-cell adhesions also co...

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Molecular organization of the uvomorulin-catenin complex.

Abstract: Abstract. The Cal+-dependent cell adhesion molecule uvomorulin is a member of the cadherin gene family.

Cited by 352 publications

References 26 publications

N‐cadherin mediates sertoli cell‐spermatogenic cell adhesion

N‐cadherin mediates sertoli cell‐spermatogenic cell adhesion

Ectopic Expression of PA2.26 Antigen in Epidermal Keratinocytes Leads to Destabilization of Adherens Junctions and Malignant Progression

Depletion of E-Cadherin Disrupts Establishment but Not Maintenance of Cell Junctions in Madin-Darby Canine Kidney Epithelial Cells

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