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)

Nectin and afadin constitute a novel intercellular adhesion system that organizes adherens junctions in cooperation with the cadherin-catenin system in epithelial cells. Nectin is a Ca(2+)-independent immunoglobulin-like adhesion molecule and afadin is an actin filament (F-actin)-binding protein that connects nectin to the actin cytoskeleton. At the puncta adhaerentia junctions (PAs) between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of the adult mouse hippocampus, the nectin-afadin system also colocalizes with the cadherin-catenin system and has a role in the formation of synapses. ZO-1 is another F-actin-binding protein that localizes at tight junctions (TJs) and connects claudin to the actin cytoskeleton in epithelial cells. The nectin-afadin system is able to recruit ZO-1 to the nectin-based cell-cell adhesion sites in nonepithelial cells that have no TJs. In the present study, we investigated the localization of ZO-1 in the mouse hippocampus. Immunofluorescence and immunoelectron microscopy revealed that ZO-1 also localized at the PAs between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of the adult mouse hippocampus, as described for afadin. ZO-1 colocalized with afadin during the development of synaptic junctions and PAs. Microbeads coated with the extracellular fragment of nectin, which interacts with cellular nectin, recruited both afadin and ZO-1 to the bead-cell contact sites in cultured rat hippocampal neurons. These results indicate that ZO-1 colocalizes with nectin and afadin at the PAs and that the nectin-afadin system is involved in the localization of ZO-1.
 ...
PMID:Nectin-dependent localization of ZO-1 at puncta adhaerentia junctions between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of adult mouse hippocampus. 1271 11

An in vivo model was used to investigate the regulation of tight junction (TJ) dynamics in the testis when adult rats were treated with CdCl(2). It was shown that the CdCl(2)-induced disruption of the blood-testis barrier (BTB) associated with a transient induction in testicular TGF-beta2 and TGF-beta3 (but not TGF-beta1) and the phosphorylated p38 mitogen activated protein (MAP) kinase, concomitant with a loss of occludin and zonula occludens-1 (ZO-1) from the BTB site in the seminiferous epithelium. These results suggest that BTB dynamics in vivo are regulated by TGF-beta2/-beta3 via the p38 MAP kinase pathway. Indeed, SB202190, a specific p38 MAP kinase inhibitor, blocked the CdCl(2)-induced occludin and ZO-1 loss from the BTB. This result clearly illustrates that CdCl(2) mediates its BTB disruptive effects via the TGF-beta3/p38 MAP kinase signaling pathway. Besides, this CdCl(2)-induced occludin and ZO-1 loss from the BTB also associated with a significant loss of the cadherin/catenin and the nectin/afadin protein complexes at the site of cell-cell actin-based adherens junctions (AJs). An induction of alpha(2)-macroglobulin (a non-specific protease inhibitor) was also observed during BTB damage and when the seminiferous epithelium was being depleted of germ cells. These data illustrate that a primary disruption of the BTB can lead to a secondary loss of cell adhesion function at the site of AJs, concomitant with an induction in protease inhibitor, which apparently is used to protect the epithelium from unwanted proteolysis. alpha(2)-Macroglobulin was also shown to associate physically with TGF-beta3, afadin and nectin 3, but not occludin, E-cadherin or N-cadherin, indicating its possible role in junction restructuring in vivo. Additionally, the use of SB202190 to block the TGF-beta3/p-38 MAP kinase pathway also prevented the CdCl(2)-induced loss of cadherin/catenin and nectin/afadin protein complexes from the AJ sites, yet it had no apparent effect on alpha(2)-macroglobulin. These results demonstrate for the first time that the TGF-beta3/p38 MAP kinase signaling pathway is being used to regulate both TJ and AJ dynamics in the testis, mediated by the effects of TGF-beta3 on TJ- and AJ-integral membrane proteins and adaptors, but not protease inhibitors.
 ...
PMID:Regulation of blood-testis barrier dynamics: an in vivo study. 1473 53

Nectins are Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecules that are involved in formation of cadherin-based adherens junctions (AJs). The nectin-based cell-cell adhesion induces activation of Cdc42 and Rac small G proteins, which eventually enhances the formation of AJs through reorganization of the actin cytoskeleton. Although evidence has accumulated that nectins recruit cadherins to the nectin-based cell-cell adhesion sites through their cytoplasm-associated proteins, afadin and catenins, it is not fully understood how nectins are physically associated with cadherins. Here we identified a rat counterpart of the human LIM domain only 7 (LMO7) as an afadin- and alpha-actinin-binding protein. Rat LMO7 has two splice variants, LMO7a and LMO7b, consisting of 1,729 and 1,395 amino acids, respectively. LMO7 has calponin homology, PDZ, and LIM domains. Western blotting revealed that LMO7 was expressed ubiquitously in various rat tissues. Immunofluorescence and immunoelectron microscopy revealed that LMO7 localized at cell-cell AJs, where afadin localized, in epithelial cells of rat gallbladder. In addition, LMO7 localized at the cytoplasmic faces of apical membranes in the same epithelial cells. We furthermore revealed that LMO7 bound alpha-actinin, an actin filament-bundling protein, which bound to alpha-catenin. Immunoprecipitation analysis revealed that LMO7 was associated with both the nectin-afadin and E-cadherin-catenin systems. LMO7 was assembled at the cell-cell adhesion sites after both the nectin-afadin and E-cadherin-catenin systems had been assembled. These results indicate that LMO7 is an afadin- and alpha-actinin-binding protein that connects the nectin-afadin and E-cadherin-catenin systems through alpha-actinin.
 ...
PMID:Involvement of LMO7 in the association of two cell-cell adhesion molecules, nectin and E-cadherin, through afadin and alpha-actinin in epithelial cells. 1514 Aug 94

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.
 ...
PMID:Protein kinases and adherens junction dynamics in the seminiferous epithelium of the rat testis. 1538 20

A plethora of evidence supports the role of cyclic nucleotides in junction restructuring. For instance, studies have shown cGMP to be a key regulator of junction assembly and disassembly in different in vitro and in vivo systems. In this study, we examine the role of soluble guanylate cyclase (sGC) in junction restructuring in the seminiferous epithelium of the rat testis. First, the interaction of soluble guanylate cyclase beta1 (sGCbeta1; sGC is a heterodimer comprised of an alpha and a beta subunit) with proteins that constitute adherens and tight junctions in the testis was demonstrated. By immunoprecipitation, sGCbeta1 was found to associate with occludin, JAM-A, and ZO-1, as well as with cadherin, catenin, nectin, afadin, ponsin, and espin, suggestive of its role in cell junction dynamics. These results were corroborated in part by immunohistochemistry experiments, which revealed that the localization of sGCbeta1 was largely restricted to the site of the apical and basal ectoplasmic specialization. Next, the role of sGC in junction dynamics was addressed by using an in vivo model of junction restructuring. Administration of Adjudin--a chemical entity known to specifically perturb adhesion between Sertoli and germ cells (i.e., round and elongate(ing) spermatids and most spermatocytes)--resulted in a approximately 1.5-fold increase in sGCbeta1, coinciding with the loss of germ cells from the epithelium. More importantly, the ability of sGCbeta1 to associate with cadherin increased approximately three-fold during Adjudin-mediated restructuring of Sertoli-germ cell junctions, whereas its interaction with tight junction proteins (i.e., occludin and ZO-1) decreased. Taken collectively, these results suggest that sGC participates in the remodeling of cell junctions during spermatogenesis.
 ...
PMID:Adjudin-mediated junction restructuring in the seminiferous epithelium leads to displacement of soluble guanylate cyclase from adherens junctions. 1654 75

AlphaT-catenin is a recently identified member of the alpha-catenin family of cell-cell adhesion molecules. For decades it was thought that alpha-catenins mediate solid cell-cell adhesion by linking the cadherin-mediated cell-cell adhesion complex with the actin cytoskeleton. However, the roles of alpha-catenins in this classical adhesion model have been questioned recently. AlphaT-catenin has a restricted expression pattern, in contrast to the ubiquitously expressed alphaE-catenin. High levels of alphaT-catenin were detected in heart and testis. Northern and Western blot experiments indicated that besides the standard full-length alphaT-catenin transcript, smaller alternative transcripts are expressed in testis. We report the cloning of two alternative transcripts of the mouse alphaT-catenin gene (transcript-B and -X), both of which are expressed in a testis-restricted manner from two putative alternative promoters. Alternative transcript-X encodes a smaller protein, isoform-X, which lacks the amino-terminal beta-catenin binding domain of the standard mouse alphaT-catenin protein, and is therefore unable to restore cell-cell adhesion in an alpha-catenin-negative colon carcinoma cell line. Immunohistochemical analysis showed specific localization of the alphaT-catenin isoform-X in the differentiating germ cells. In contrast to the standard full-length alphaT-catenin protein, this shortened isoform-X can bind to l-afadin, an important component of the nectin/afadin/ponsin adhesion complex that reportedly is essential for spermatogenesis.
 ...
PMID:Truncated isoform of mouse alphaT-catenin is testis-restricted in expression and function. 1718 52

Nectins are cell adhesion molecules that, together with the intracellular binding partner afadin, mediate adhesion and signaling at a variety of intercellular junctions. In this work we studied the distribution of nectin-1 and afadin during hippocampal synapse formation using cultured primary hippocampal neurons. Nectin-1 and afadin cluster at developing synapses between hippocampal neurons. These nectin-afadin clusters uniformly colocalize with N-cadherin-catenin pairs, suggesting that formation of developing synapses involves participation of both bimolecular systems. Nectin-1 is initially expressed at excitatory and inhibitory synapses but is progressively lost at inhibitory synapses during their maturation. Treatment of neurons with actin depolymerizing agents disrupts the synaptically localized nectin-1 and afadin cluster at an early stage and elicits nectin-1 ectodomain shedding. These data indicate that the synaptic localization of nectin-1 and l-afadin are F-actin-dependent and that the shedding of nectin-1 is a mechanism contributing to synaptic plasticity.
 ...
PMID:Temporal and spatial localization of nectin-1 and l-afadin during synaptogenesis in hippocampal neurons. 1818 Nov 41

The nectin-afadin complex is involved in the formation of cell-cell junctions, such as adherens junctions (AJs) and tight junctions (TJs). Nectins are Ca(2+)-independent immunoglobulin-like cell-cell adhesion molecules, whereas afadin is an intracellular nectin-binding protein that connects nectins to the cadherin-catenin system at AJs and to the claudin-zona-occludens (ZO) protein system at TJs. Afadin(-/-) mice show embryonic lethality, resulting from impaired migration and improper differentiation of cells due to disorganization of cell-cell junctions during gastrulation. However, it remains to be elucidated whether disruption of afadin affects apoptosis. In the present study, we first found that embryoid bodies derived from afadin-knockout embryonic stem (ES) cells contained many more apoptotic cells than those derived from wild-type ES cells. We also revealed that apoptosis induced by serum starvation or Fas-ligand stimulation was increased in cultured NIH3T3 cells when afadin or nectin-3 was knocked down. The nectin-afadin complex was involved in the platelet-derived growth factor (PDGF)-induced activation of phosphatidylinositol 3-kinase (PI3K)-Akt signaling for cell survival. This complex was associated with PDGF receptor on the plasma membrane at cell-cell adhesion sites. Thus, the nectin-afadin complex is involved in PDGF-induced cell survival, at least through the PI3K-Akt signaling pathway.
 ...
PMID:Involvement of the nectin-afadin complex in PDGF-induced cell survival. 1850 95

The LIM domain only protein 7 (LMO7), a member of the PDZ and LIM domain-containing protein family is a candidate gene with possible roles in embryonic development and breast cancer progression. LMO7 has been linked to actin cytoskeleton organization through nectin/afadin and to cell-cell adhesion by means of E-cadherin/catenin. In addition, LMO7 has been shown to regulate transcription of the nuclear membrane protein Emerin and other muscle relevant genes. In this study, we used in situ hybridization to investigate LMO7 expression during embryonic development in three widely used vertebrate model species: the zebrafish, the chicken and the mouse. Our temporal and spatial gene expression analysis revealed both common and distinct patterns between these species. In mouse and chicken embryos we found expression in the outflow tract, the inflow tract, the pro-epicardial organ and the second heart field, structures highly important in the developing heart. Furthermore, gene knockdown experiments in zebrafish embryos resulted in severe defects in heart development with effects on the conduction system and on heart localization. In summary, we present here the first developmental study of LMO7. We reveal the temporal and spatial expression patterns of this important gene during mouse, chicken and fish development and our findings suggest essential functions for LMO7 during vertebrate heart development.
 ...
PMID:The lim domain only protein 7 is important in zebrafish heart development. 1903 55

In the hippocampus, synapses are formed between mossy fiber terminals and CA3 pyramidal cell dendrites and comprise highly developed synaptic junctions (SJs) and puncta adherentia junctions (PAJs). Dynamic remodeling of synapses in the hippocampus is implicated in learning and memory. Components of both the nectin-afadin and cadherin-catenin cell adhesion systems exclusively accumulate at PAJs. We investigated the role of afadin at synapses in mice in which the afadin gene was conditionally inactivated in hippocampal neurons. In these mutant mice, the signals for not only nectins, but also N-cadherin and beta-catenin, were hardly detected in the CA3 area, in addition to loss of the signal for afadin, resulting in disruption of PAJs. Ultrastructural analysis revealed an increase in the number of perforated synapses, suggesting the instability of SJs. These results indicate that afadin is involved not only in the assembly of nectins and cadherins at synapses, but also in synaptic remodeling.
 ...
PMID:Involvement of afadin in the formation and remodeling of synapses in the hippocampus. 1948 Oct 57


<< Previous 1 2 3 4 Next >>