SEARCH · PubMed Health

Results for “Delta Catenin”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2006

Presenilin-1 inhibits delta-catenin-induced cellular branching and promotes delta-catenin processing and turnover.

Although delta-catenin/neural plakophilin-related armadillo protein (NPRAP) was reported to interact with presenilin-1 (PS-1), the effects of PS-1 on delta-catenin have not been established. In this study, we report that overexpression of PS-1 inhibits the delta-catenin-induced dendrite-like morphological changes in NIH 3T3 cells and promotes delta-catenin processing and turnover. The effects of PS-1 on endogenous delta-catenin processing were confirmed in hippocampal neurons overexpressing PS-1, as well as in the transgenic mice expressing the disease-causing mutant PS-1 (M146V). In addition, disease-causing mutant PS-1 (M146V and L286V) enhanced delta-catenin processing, whereas PS-1/gamma-secretase inhibitors could block the formation of processed forms of delta-catenin. Together, our findings suggest that PS-1 can affect delta-catenin-induced morphogenesis possibly through the regulation of its processing and stability.

Alzheimer Disease↗

PubMed2002

The Erbin PDZ domain binds with high affinity and specificity to the carboxyl termini of delta-catenin and ARVCF.

Erbin is a recently described member of the LAP (leucine-rich repeat and PDZ domain) protein family. We used a C-terminally displayed phage peptide library to identify optimal ligands for the Erbin PDZ domain. Phage-selected peptides were type 1 PDZ ligands that bound with high affinity and specificity to the Erbin PDZ domain in vitro. These peptides most closely resembled the C-terminal PDZ domain-binding motifs of three p120-related catenins: delta-catenin, ARVCF, and p0071 (DSWV-COOH). Analysis of the interactions of the Erbin PDZ domain with synthetic peptides matching the C termini of ARVCF or delta-catenin also demonstrated specific high affinity binding. We characterized the interactions between the Erbin PDZ domain and both ARVCF and delta-catenin in vitro and in vivo. The Erbin PDZ domain co-localized and coprecipitated with ARVCF or delta-catenin complexed with beta-catenin and E/N-cadherin. Mutagenesis and peptide competition experiments showed that the association of Erbin with the cadherin-catenin complex was mediated by the interaction of its PDZ domain with the C-terminal PDZ domain-binding motifs (DSWV-COOH) of ARVCF and delta-catenin. Finally, we showed that endogenous delta-catenin and Erbin co-localized in and co-immunoprecipitated from neurons. These results suggest that delta-catenin and ARVCF may function to mediate the association of Erbin with the junctional cadherin-catenin complex. They also demonstrate that C-terminal phage-display technology can be used to predict physiologically relevant ligands for PDZ domains.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Deletion of the neuron-specific protein delta-catenin leads to severe cognitive and synaptic dysfunction.

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.

Analysis of Variance↗

PubMed2003

Dual regulation of neuronal morphogenesis by a delta-catenin-cortactin complex and Rho.

Delta-catenin is a neuronal protein that contains 10 Armadillo motifs and binds to the juxtamembrane segment of classical cadherins. We report that delta-catenin interacts with cortactin in a tyrosine phosphorylation-dependent manner. This interaction occurs within a region of the delta-catenin sequence that is also essential for the neurite elongation effects. Src family kinases can phosphorylate delta-catenin and bind to delta-catenin through its polyproline tract. Under conditions when tyrosine phosphorylation is reduced, delta-catenin binds to cortactin and cells extend unbranched primary processes. Conversely, increasing tyrosine phosphorylation disrupts the delta-catenin-cortactin complex. When RhoA is inhibited, delta-catenin enhances the effects of Rho inhibition on branching. We conclude that delta-catenin contributes to setting a balance between neurite elongation and branching in the elaboration of a complex dendritic tree.

Amino Acid Sequence↗

PubMed2002

Glutamate-induced delta-catenin redistribution and dissociation from postsynaptic receptor complexes.

Delta-catenin (or neural plakophilin-related arm-repeat protein/neurojungin) is primarily a brain specific member of the p120(ctn) subfamily of armadillo/beta-catenin proteins that play important roles in neuronal development. Our previous studies have shown that the ectopic expression of delta-catenin induces the formation of dendrite-like extensions and that the overexpression of delta-catenin promotes dendritic branching and increases spine density. Here we demonstrate that delta-catenin displays a dendritic distribution pattern in the adult mouse brain and is co-enriched with postsynaptic density-95 (PSD-95) in the detergent insoluble postsynaptic scaffolds. Delta-catenin forms stable complexes with excitatory neurotransmitter receptors including ionotropic N-methyl-D-aspartic acid receptor 2A (NR2A), metabotropic glutamate receptor 1alpha (mGluR1alpha), as well as PSD-95 in vivo. In cultured primary embryonic neurons, delta-catenin clusters co-distribute with filamentous actin and resist detergent extraction. In dissociated hippocampal neurons overexpressing delta-catenin, glutamate stimulation leads to a rapid redistribution of delta-catenin that can be attenuated by 6-cyano-7-nitroquinoxaline-2,3-dione and dizocilpine, selective inhibitors of ionotropic glutamate receptors. Upon glutamate receptor activation, delta-catenin becomes down-regulated and its association with NR2A and mGluR1alpha in cultured neurons is diminished. These findings support a possible functional connection between delta-catenin and the glutamatergic excitatory synaptic signaling pathway during neuronal development.

Actin Cytoskeleton↗

PubMed2005

Delta-catenin at the synaptic-adherens junction.

Delta-catenin belongs to the p120-catenin (p120(ctn)) protein family, which is characterized by ten, characteristically spaced Armadillo repeats that bind to the juxtamembrane segment of the classical cadherins. Delta-catenin is the only member of this family that is expressed specifically in neurons, where it binds to PDZ domain proteins in the post-synaptic compartment. As a component of both adherens and synaptic junctions, delta-catenin can link the adherens junction to the synapse and, thereby, coordinate synaptic input with changes in the adherens junction. By virtue of its restriction to the post-synaptic area, delta-catenin creates an asymmetric adherens junction in the region of the synapse. The crucial nature of the specialized function of delta-catenin in neurons is demonstrated by a targeted gene mutation, which causes deficits in learning and in synaptic plasticity. Taken together, recent evidence indicates that delta-catenin is a sensor of synaptic activity and implements activity-related morphological changes at the synapse.

Adherens Junctions↗

PubMed1999

delta-catenin, an adhesive junction-associated protein which promotes cell scattering.

The classical adherens junction that holds epithelial cells together consists of a protein complex in which members of the cadherin family linked to various catenins are the principal components. delta-catenin is a mammalian brain protein in the Armadillo repeat superfamily with sequence similarity to the adherens junction protein p120(ctn). We found that delta-catenin can be immunoprecipitated as a complex with other components of the adherens junction, including cadherin and beta-catenin, from transfected cells and brain. The interaction with cadherin involves direct contact within the highly conserved juxtamembrane region of the COOH terminus, where p120(ctn) also binds. In developing mouse brain, staining with delta-catenin antibodies is prominent towards the apical boundary of the neuroepithelial cells in the ventricular zone. When transfected into Madin-Darby canine kidney (MDCK) epithelial cells delta-catenin colocalized with cadherin, p120(ctn), and beta-catenin. The Arm domain alone was sufficient for achieving localization and coimmunoprecipitation with cadherin. The ectopic expression of delta-catenin in MDCK cells altered their morphology, induced the elaboration of lamellipodia, interfered with monolayer formation, and increased scattering in response to hepatocyte growth factor treatment. We propose that delta-catenin can regulate adhesion molecules to implement the organization of large cellular arrays necessary for tissue morphogenesis.

Animals↗

PubMed2004

Regulation of the rapsyn promoter by kaiso and delta-catenin.

Rapsyn is a synapse-specific protein that is required for clustering acetylcholine receptors at the neuromuscular junction. Analysis of the rapsyn promoter revealed a consensus site for the transcription factor Kaiso within a region that is mutated in a subset of patients with congenital myasthenic syndrome. Kaiso is a POZ-zinc finger family transcription factor which recognizes the specific core consensus sequence CTGCNA (where N is any nucleotide). Previously, the only known binding partner for Kaiso was the cell adhesion cofactor, p120 catenin. Here we show that delta-catenin, a brain-specific member of the p120 catenin subfamily, forms a complex with Kaiso. Antibodies against Kaiso and delta-catenin recognize proteins in the nuclei of C2C12 myocytes and at the postsynaptic domain of the mouse neuromuscular junction. Endogenous Kaiso in C2C12 cells coprecipitates with the rapsyn promoter in vivo as shown by chromatin immunoprecipitation assay. Minimal promoter assays demonstrated that the rapsyn promoter can be activated by Kaiso and delta-catenin; this activation is apparently muscle specific. These results provide the first experimental evidence that rapsyn is a direct sequence-specific target of Kaiso and delta-catenin. We propose a new model of synapse-specific transcription that involves the interaction of Kaiso, delta-catenin, and myogenic transcription factors at the neuromuscular junction.

Active Transport, Cell Nucleus↗

PubMed2006

Pax6 is required for delta-catenin/neurojugin expression during retinal, cerebellar and cortical development in mice.

The transcription factor Pax6 regulates multiple aspects of central nervous system (CNS) development. At the cellular level, the Pax6 mutation was reported to affect homophilic and heterophilic cellular adhesion, neuron polarity and neurite outgrowth. These abnormalities were observed in multiple regions of Pax6-mutant CNS, suggesting a common function for Pax6 in regulating cytoskeletal dynamics. However, target genes mediating Pax6 function in cytoskeletal dynamics remain largely unknown. Using DNA microarrays, we identified delta-catenin (delta-catenin /neurojugin) as a potential direct target of Pax6 in the CNS. delta-catenin encodes a large cytoskeletal protein that localizes at adherens junction in the CNS and that can modulate neurite outgrowth and N-cadherin turnover. delta-catenin was found to be co-expressed with Pax6 in several regions of the developing CNS. In Pax6 mutant embryos, delta-catenin expression was severely reduced in the optic vesicle neural ectoderm, in the ventricular zone of the neocortex and in the external granule layer of the cerebellum. We identified a Pax6 binding site in delta-catenin promoter that is conserved between mice and humans and which is effectively bound by Pax6 in vitro. Our results suggest that Pax6 regulates delta-catenin expression during CNS development in mice.

Animals↗

PubMed2002

Brain armadillo protein delta-catenin interacts with Abl tyrosine kinase and modulates cellular morphogenesis in response to growth factors.

delta-Catenin associates with adhesive junctions and facilitates cellular morphogenesis (Lu et al., 1999). Here we show that delta-catenin colocalizes with actin filaments and Abl tyrosine kinase in the growth cones of cultured hippocampal neurons. PC12 cells induced to express delta-catenin show accelerated neurite extension upon nerve growth factor (NGF) stimulation. STI571, an Abl family kinase inhibitor, further accentuates these stimulatory effects. delta-Catenin is a potent substrate for Abl in vitro using an immunocomplex assay and most of the Abl-induced tyrosine phosphorylation within cells is present in the N-terminus of delta-catenin. When delta-catenin-expressing epithelial cells are induced to scatter in response to hepatocyte growth factor (HGF), STI571 leads to the rapid redistribution of delta-catenin and changes in cellular morphology. We suggest that delta-catenin is a possible Abl substrate and acts downstream of Abl to orchestrate actin-based cellular morphogenesis.

Actin Cytoskeleton↗

PubMed2000

delta-catenin is a nervous system-specific adherens junction protein which undergoes dynamic relocalization during development.

delta-catenin is a member of the Armadillo repeat family and component of the adherens junction discovered in a two-hybrid assay as a bona fide interactor with presenilin-1 (Zhou et al., [1997], NeuroReport 8:2085-2090), a protein which carries mutations that cause familial Alzheimer's disease. The expression pattern of delta-catenin was mapped between embryonic day 10 (E10) and adulthood by Northern blots, in situ hybridization and immunohistochemistry in the mouse. In development, delta-catenin is dynamically regulated with respect to its site of expression. It is first expressed within proliferating neuronal progenitor cells of the neuroepithelium, becomes down-regulated during neuronal migration, and is later reexpressed in the dendritic compartment of postmitotic neurons. In the mouse, delta-catenin mRNA is expressed by E10, increases and peaks at postnatal day (P)7, with lower levels in adulthood. In the developing neocortex, delta-catenin mRNA is strongly expressed in the proliferative ventricular zone and the developing cortical plate, yet is conspicuously less prominent in the intermediate zone, which contains migrating cortical neurons, delta-catenin protein forms a honeycomb pattern in the neuroepithelium by labeling the cell periphery in a typical adherens junction pattern. By E18, delta-catenin expression shifts primarily to nascent apical dendrites, a pattern that continues through adulthood. The dynamic relocalization of delta-catenin expression during development, taken together with previously published data which described a role for delta-catenin in cell motility (Lu et al., [1999] J. Cell. Biol. 144:519-532), suggests the hypothesis that delta-catenin regulation is closely linked to neuronal migration and may play a role in the establishment of mature dendritic relationships in the neuropil.

Animals↗

PubMed2005

Increased expression of delta-catenin/neural plakophilin-related armadillo protein is associated with the down-regulation and redistribution of E-cadherin and p120ctn in human prostate cancer.

delta-Catenin, or neural plakophilin-related armadillo protein, is a unique armadillo domain-containing protein in that it is neural-specific and primarily expressed in the brain. However, our recent analysis of the human genome revealed a consistent association of delta-catenin messenger RNA sequences with malignant cells, although the significance of these findings was unclear. In this study, we report that a number of delta-catenin epitopes were expressed in human prostate cancer cells. Western blot and tissue microarray revealed a close association between increased delta-catenin expression and human primary prostatic adenocarcinomas. The analyses of 90 human prostate cancer and 90 benign prostate tissue samples demonstrated that an estimated 85% of prostatic adenocarcinomas showed enhanced delta-catenin immunoreactivity. delta-Catenin expression increased with prognostically significant increased Gleason scores. By analyzing the same tumor cell clusters using consecutive sections, we showed that an increased delta-catenin immunoreactivity was accompanied by the down-regulation and redistribution of E-cadherin and p120ctn, major cell junction proteins whose inactivation is frequently associated with cancer progression. Furthermore, overexpression of delta-catenin in tumorigenic CWR-R1 cells that are derived from human prostate cancer xenograft resulted in reduced immunoreactivity for E-cadherin and p120ctn at the cell-cell junction. This is the first study comparing overexpression of delta-catenin with the E-cadherin/catenin system in cancer and shows that delta-catenin may be intimately involved in regulating E-cadherin/p120ctn cell-cell adhesion in prostate cancer progression.

Adenocarcinoma↗

PubMed2000

Hemizygosity of delta-catenin (CTNND2) is associated with severe mental retardation in cri-du-chat syndrome.

Delta-catenin is an adherens junction protein involved in cell motility and expressed early in neuronal development. It was discovered as an interactor with presenilin-1. The genomic structure of the human delta-catenin gene (Human Gene Nomenclature Committee-approved symbol CTNND2) was determined and mapped to 5p15.2. A deletion of this chromosomal region has been associated with the cri-du-chat syndrome (CDCS), a segmental aneusomy syndrome of 5p that is associated with an unusual high-pitched cry at birth, facial dysmorphology, poor growth, and severe mental retardation. delta-catenin maps to a specific region in 5p15.2 that has been implicated in the mental retardation phenotype. The breakpoints in patients with 5p terminal deletions were characterized with respect to the severity of mental retardation and the physical location of the delta-catenin gene. A strong correlation was found between the hemizygous loss of delta-catenin and severe mental retardation. These findings and the properties of delta-catenin as a neuronal-specific protein, expressed early in development and involved in cell motility, support its role in the mental retardation of CDCS when present in only one copy.

Armadillo Domain Proteins↗

PubMed2002

Expression analysis of delta-catenin and prostate-specific membrane antigen: their potential as diagnostic markers for prostate cancer.

The current approach to prostate cancer diagnosis has major limitations including the inability of prostate-specific antigen (PSA) assays to accurately differentiate between prostate cancer and benign prostate hyperplasia (BPH) and the imprecision of transrectal ultrasound (TRUS) biopsy sampling. We have employed cDNA microarray screening to compare gene expression patterns in BPH and tumour samples to identify expression markers that may be useful in discriminating between these conditions. Screening of 3 individual cDNA arrays identified 8 genes with expression 3-fold greater in 6 tumour tissues than in 1 nontumour sample and 1 BPH sample. Real-time PCR was used to confirm the overexpression of these 8 genes and 12 genes selected from the literature against a panel of 17 tumours and 11 BPH samples. Two genes, delta-catenin (delta-catenin; CTNND2) and prostate-specific membrane antigen (PSMA; FOLH1), were significantly overexpressed in prostate cancer compared to BPH. Prostate epithelial cells stained positively for delta-catenin and PSMA in our prostate cancer tissues, whereas the majority of our BPH tissues were negative for both markers. Thus we have identified delta-catenin (not previously associated with prostatic adenocarcinoma) and confirmed the potential of PSMA as potential candidates for the diagnosis and management of prostate cancer.

Adult↗

PubMed2004

Delta-catenin/NPRAP (neural plakophilin-related armadillo repeat protein) interacts with and activates sphingosine kinase 1.

Sphingosine kinase (SPHK) is a key enzyme catalysing the formation of sphingosine 1-phosphate (SPP), a lipid messenger that is implicated in the regulation of a wide variety of important cellular events acting through intracellular, as well as extracellular, mechanisms. However, the molecular mechanism of intracellular actions of SPP remains unclear. Here, we have identified delta-catenin/NPRAP (neural plakophilin-related armadillo repeat protein) as a potential binding partner for SPHK1 by yeast two-hybrid screening. From co-immunoprecipitation analyses, the C-terminal portion of delta-catenin/NPRAP containing the seventh to tenth armadillo repeats was found to be required for interaction with SPHK1. Endogenous delta-catenin/NPRAP was co-localized with endogenous SPHK1 and transfected delta-catenin/NPRAP was co-localized with transfected SPHK1 in dissociated rat hippocampal neurons. MDCK (Madin-Darby canine kidney) cells stably expressing delta-catenin/NPRAP contained elevated levels of intracellular SPP. In a purified system delta-catenin/NPRAP stimulated SPHK1 in a dose-dependent manner. Furthermore, delta-catenin/NPRAP-induced increased cell motility in MDCK cells was completely inhibited by dimethylsphingosine, a specific inhibitor of SPHK1. These results strongly suggest that at least some of delta-catenin/NPRAP functions, including increased cell motility, are mediated by an SPHK-SPP signalling pathway.

Animals↗

PubMed2001

Densin-180 interacts with delta-catenin/neural plakophilin-related armadillo repeat protein at synapses.

Densin-180, a protein purified from the postsynaptic density fraction of the rat forebrain, is the founding member of a newly described family of proteins termed the LAP (leucine-rich repeats and PSD-95/Dlg-A/ZO-1 (PDZ) domains) family that plays essential roles in establishment of cell polarity. To identify Densin-180-binding proteins, we screened a yeast two-hybrid library using the carboxyl-terminal fragment of Densin-180 containing PDZ domain as bait, and we isolated delta-catenin/neural plakophilin-related armadillo repeat protein (NPRAP) as a Densin-180-interacting protein. delta-catenin/NPRAP, a member of the armadillo repeat family, is a nervous system-specific adherens junction protein originally discovered as an interactor with presenilin-1, a protein involved in Alzheimer's disease. Densin-180 PDZ domain binds the COOH terminus of delta-catenin/NPRAP containing the PDZ domain-binding sequence. Endogenous Densin-180 was co-immunoprecipitated with delta-catenin/NPRAP and N-cadherin. Although Densin-180 was reported to be a transmembrane protein, Densin-180 was not accessible to surface biotinylation in dissociated hippocampal neurons; hence Densin-180 may be a cytosolic protein. Densin-180 co-localized with delta-catenin/NPRAP at synapses in delta-catenin/NPRAP and may be involved in organization of the synaptic cell-cell junction through interaction with the delta-catenin/NPRAP-N-cadherin complex.

Animals↗

PubMed2002

Dendrite-like process formation and cytoskeletal remodeling regulated by delta-catenin expression.

Actin- and microtubule-mediated changes in cell shape are essential for many cellular activities. However, the molecular mechanisms underlying the interplay between the two are complex and remain obscure. Here we show that the expression of delta-catenin (or NPRAP/Neurojungin), a member of p120(ctn) subfamily of armadillo proteins can induce the branching of dendrite-like processes in 3T3 cells and enhance dendritic morphogenesis in primary hippocampal neurons. This induction of branching phenotype involves initially the disruption of filamentous actin, and requires the growth of microtubules. The carboxyl-terminal truncation mutant of delta-catenin can cluster and redistribute the full-length protein, and dominantly inhibit its branching effect. delta-Catenin forms protein complexes and can bind directly to actin in vitro. The carboxyl-terminal truncation of delta-catenin does not interfere with its actin-binding capability; therefore the actin interaction alone is not sufficient for the induction of dendrite-like processes. When delta-catenin-transformed cells establish elaborate dendrite-like branches, the main cellular processes become stabilized and resist the disruption of both actin filaments and microtubules, as determined by fluorescent light microscopy and time-lapse recording analyses. We suggest that delta-catenin can effect a biphasic cytoskeletal remodeling event which differentially regulates actin and microtubules and promotes cellular morphogenesis.

3T3 Cells↗

PubMed2007

cdk5 modulates beta- and delta-catenin/Pin1 interactions in neuronal cells.

The cdk5/p35 complex has been implicated in a variety of functions related to brain development, including axonal outgrown and neuronal migration. In this study, by co-immunoprecipitation and pull-down experiments, we have shown that the cdk5/p35 complex associates with and phosphorylates the neuronal delta-catenin. Immunocytochemical studies of delta-catenin and the cdk5-activator p35 in primary cortical neurons indicated that these proteins co-localize in the cell body of neuronal cells. In addition, cdk5 co-localized with beta-catenin in the cell-cell contacts and plasma membrane of undifferentiated and differentiated N2A cells. In this context, we identified Ser(191) and Ser(246) on beta-catenin structure as specific phosphorylation sites for cdk5/p35 complex. Moreover, Pin1, a peptidyl-prolyl isomerase (PPIase) directly bound to both, beta- and delta-catenin, once they have been phosphorylated by the cdk5/p35 complex. Studies indicate that the cdk5/p35 protein kinase system is directly involved in the regulatory mechanisms of neuronal beta- and delta-catenin.

Adaptor Proteins, Signal Transducing↗