Classic cadherins are transmembrane receptors involved in cell type-specific calcium-dependent intercellular adhesion. The specificity of adhesion is mediated by homophilic interactions between cadherins extending from opposing cell surfaces. In addition, classic cadherins can self-associate forming lateral dimers. Whereas it is widely excepted that lateral dimerization of cadherins is critical for adhesion, details of this process are not known. Yet, no evidence for physical association between different classic cadherins in cells expressing complex cadherin patterns has been reported. To study lateral and adhesive intercadherin interactions, we examined interactions between two classic cadherins, E- and P-cadherins, in epithelial A-431 cells co-producing both proteins. We showed that these cells exhibited heterocomplexes consisting of laterally assembled E- and P-cadherins. These complexes were formed by a mechanism involving Trp(156) of E-cadherin. Removal of calcium ions from the culture ...
Cadherins are a family of transmembrane proteins formed from multiple repeats of cadherin-specific motif (a recurrent molecular sequence) and also share a large extracellular domain. Cadherins are classified into two groups: Classical Cadherins and Protocadherins. The main difference between the two groups of cadherins is the classical cadherins contain five cadherin repeats with the third (EC3) and the fifth (EC5) repeat having very specific features. The protocadherins do not share the same features of the EC3 and EC5 units; are longer than five repeats long; and the sequences are very similar to each other. As a result of these differences, the classical cadherins are very specific and do not adhere to a large number of different ECM proteins, whereas protocadherins are much more flexible in their attachments. Classical cadherins are known to only be found in vertebrates so far, while protocadherins are found in planaria, hydra, Drosophila, and various mammals. Cadherins rely heavily on ...
P-cadherin is a subclass of Ca2+-dependent cell-cell adhesion molecules present in mouse placenta, where its localization suggests a function of connecting the embryo to the uterus (Nose, A., and M. Takeichi. 1986. J. Cell Biol. 103:2649-2658). We recently identified a human cadherin detected by an mAb capable of disrupting cell-cell adhesion of A-431 cells, and found that it was closely related immunochemically to mouse P-cadherin. Curiously, this cadherin was undetectable in human placenta by immunohistochemical examination (Shimoyama, Y., S. Hirohashi, S. Hirano, M. Noguchi, Y. Shimosato, M. Takeichi, and O. Abe. 1989. Cancer Res. 49:2128-2133). We here report the cloning and sequencing of cDNA clone encoding the human homologue of mouse P-cadherin. The deduced amino acid sequence of the human P-cadherin consists of 829 amino acid and shows striking homology with mouse P-cadherin. On Northern blot analysis, human P-cadherin was scarcely expressed in human placenta in contrast to mouse ...
Clustered protocadherins (PCDHs) map in tandem at human chromosome 5q31 and comprise three multi-genes clusters: α-, β- and γ-PCDH. The expression of this cluster consists of a complex mechanism involving DNA hub formation through DNA-CCTC binding factor (CTCF) interaction. Methylation alterations can affect this interaction, leading to transcriptional dysregulation. In cancer, clustered PCDHs undergo a mechanism of long-range epigenetic silencing by hypermethylation. In this study, we detected frequent methylation alterations at CpG islands associated to these clustered PCDHs in all the solid tumours analysed (colorectal, gastric and biliary tract cancers, pilocytic astrocytoma), but not hematologic neoplasms such as chronic lymphocytic leukemia. Importantly, several altered CpG islands were associated with CTCF binding sites. Interestingly, our analysis revealed a hypomethylation event in pilocytic astrocytoma, suggesting that in neuronal tissue, where PCDHs are highly expressed, these genes become
Clustered protocadherins (PCDHs) map in tandem at human chromosome 5q31 and comprise three multi-genes clusters: α-, β- and γ-PCDH. The expression of this cluster consists of a complex mechanism involving DNA hub formation through DNA-CCTC binding factor (CTCF) interaction. Methylation alterations can affect this interaction, leading to transcriptional dysregulation. In cancer, clustered PCDHs undergo a mechanism of long-range epigenetic silencing by hypermethylation. In this study, we detected frequent methylation alterations at CpG islands associated to these clustered PCDHs in all the solid tumours analysed (colorectal, gastric and biliary tract cancers, pilocytic astrocytoma), but not hematologic neoplasms such as chronic lymphocytic leukemia. Importantly, several altered CpG islands were associated with CTCF binding sites. Interestingly, our analysis revealed a hypomethylation event in pilocytic astrocytoma, suggesting that in neuronal tissue, where PCDHs are highly expressed, these genes become
Detachment of cell-cell adhesion is indispensable for the first step of invasion and metastasis of cancer. This mechanism is frequently associated with the impairment of either E-cadherin expression or function. However, mechanisms of such abnormalities have not been fully elucidated. In this study, we demonstrated that the function of E-cadherin was completely abolished in the human gastric cancer cell line HSC-39, despite the high expression of E-cadherin, because of mutations in one of the E-cadherin-associated cytoplasmic proteins, beta-catenin. Although immunofluorescence staining of HSC-39 cells by using an anti-E-cadherin antibody (HECD-1) revealed the strong and uniform expression of E-cadherin on the cell surface, cell compaction and cell aggregation were not observed in this cell. Western blotting (immunoblotting) using HECD-1 exhibited a 120-kDa band which is equivalent to normal E-cadherin. Northern (RNA) blotting demonstrated a 4.7-kb band, the same as mature E-cadherin mRNA. ...
TY - JOUR. T1 - Calcium-dependent dynamics of cadherin interactions at cell-cell junctions. AU - Kim, Sally A.. AU - Tai, Chin Yin. AU - Mok, Lee Peng. AU - Mosser, Eric A.. AU - Schuman, Erin M.. PY - 2011/6/14. Y1 - 2011/6/14. N2 - Cadherins play a key role in the dynamics of cell-cell contact formation and remodeling of junctions and tissues. Cadherin-cadherin interactions are gated by extracellular Ca2+, which serves to rigidify the cadherin extracellular domains and promote trans junctional interactions. Here we describe the direct visualization and quantification of spatiotemporal dynamics of N-cadherin interactions across intercellular junctions in living cells using a genetically encodable FRET reporter system. Direct measurements of transjunctional cadherin interactions revealed a sudden, but partial, loss of homophilic interactions (τ = 1.17 ± 0.06 s-1) upon chelation of extracellular Ca2+. A cadherin mutant with reduced adhesive activity (W2A) exhibited a faster, more substantial ...
Classical cadherins mediate Ca2+-dependent intercellular adhesion and are essential for tissue morphogenesis and maintenance. They are key components of adherens junctions (AJs). In vitro studies in simple epithelial cells indicated an essential role for E-cadherin not only in the formation of AJs but also other intercellular contacts, such as desmosomes and tight junctions. In contrast, in vivo tissue specific knockout studies did not reveal a necessity of E-cadherin in the formation of intercellular junctions, raising the question if classical cadherins are necessary or if other classical cadherins can compensate for the loss of E-cadherin. Therefore, the aim of this thesis was to ask how E-cadherin regulates tight junctions and if E-cadherin has a specific function in the formation of tight junctions. In addition, the question was asked if classical cadherin function is necessary for the formation of other intercellular contacts, such as desmosomes. Using primary keratinocytes as a model for ...
Loss of the epithelial adhesion molecule E-cadherin is thought to enable metastasis by disrupting intercellular contacts-an early step in metastatic dissemination. To further investigate the molecular basis of this notion, we use two methods to inhibit E-cadherin function that distinguish between E-cadherins cell-cell adhesion and intracellular signaling functions. Whereas the disruption of cell-cell contacts alone does not enable metastasis, the loss of E-cadherin protein does, through induction of an epithelial-to-mesenchymal transition, invasiveness, and anoikis resistance. We find the E-cadherin binding partner beta-catenin to be necessary, but not sufficient, for induction of these phenotypes. In addition, gene expression analysis shows that E-cadherin loss results in the induction of multiple transcription factors, at least one of which, Twist, is necessary for E-cadherin loss-induced metastasis. These findings indicate that E-cadherin loss in tumors contributes to metastatic ...
This gene is a type II classical cadherin from the cadherin superfamily and one of three cadherin 7-like genes located in a cluster on chromosome 18. The encoded membrane protein is a calcium dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. Since disturbance of intracellular adhesion is a prerequisite for invasion and metastasis of tumor cells, cadherins are considered prime candidates for tumor suppressor genes. [provided by RefSeq, Jul 2008 ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a type II classical cadherin from the cadherin superfamily and one of three cadherin 7-like genes located in a cluster on chromosome 18. The encoded membrane protein is a calcium dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. Since disturbance of intracellular adhesion is a prerequisite for invasion and metastasis of tumor cells, cadherins are considered prime candidates for tumor suppressor genes. [provided by RefSeq, Jul 2008 ...
This gene encodes a classical cadherin of the cadherin superfamily. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature glycoprotein. This calcium-dependent cell-cell adhesion protein is comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. This gene is located in a gene cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. In addition, aberrant expression of this protein is observed in cervical adenocarcinomas. Mutations in this gene are associated with hypotrichosis with juvenile macular dystrophy and ectodermal dysplasia, ectrodactyly, and macular dystrophy syndrome (EEMS). [provided by RefSeq, Nov 2015 ...
Because AQP3 but not AQP5 was delivered to cell-cell contacts, we directly tested whether a targeting patch specific for basolateral vesicles is assembled upon E-cadherin-mediated cell-cell adhesion. Our data indicate that microtubules, the exocyst, and t-SNAREs are essential components of this lateral targeting patch. We showed that the exocyst and the t-SNARE syntaxin 4 colocalized with E-cadherin at early cell-cell contacts, and it has been shown by others that microtubule plus ends extend radially into cell-cell contacts (Stehbens et al., 2006; Shaw et al., 2007). Functional disruption of any one of these components did not interfere with the establishment of cell-cell adhesion or the localization of other components to cell-cell contact. Because there is a large amount of E-cadherin on the cell surface before cell adhesion (Adams et al. 1998), it is therefore likely that initial cell-cell adhesion does not require the delivery of E-cadherin from intracellular compartments. However, ...
Advisor: Andrés J. García, PhD (Georgia Institute of Technology). Committee: Thomas H. Barker, PhD (Georgia Institute of Technology). Andrew P. Kowalczyk, PhD (Emory University). Susan N. Thomas, PhD (Georgia Institute of Technology). Cheng Zhu, PhD (Georgia Institute of Technology). Quantitative Analyses for Cadherin-Based Cell-Cell Adhesive Force. Cell adhesion is a critical determinant of tissue architecture and tissue organization. Cadherin proteins mediate cell-cell adhesion in a calcium-dependent manner. The functional roles for cadherin proteins early in development and in adults, as well as the multiple disease phenotypes resulting from cadherin dysregulation, underscore the importance of cadherin proteins. Quantitative assessment of cadherin interaction structure, force, and interaction dynamics is not yet completely understood because of lack of experimental platforms to study cadherin proteins as well as their often-conflicting roles in a tissue-specific manner. Adhesive force ...
This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the proteins homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is expressed in brain and is putatively involved in synaptic adhesion, axon outgrowth and guidance.[7] ...
My work examines the role of a conserved tryptophan residue, Trp2, in the adhesive domain of cadherins that has been shown to be essential for their adhesive function. Structural studies have shown Trp2 to be integrated into its own cadherin domain, integrated into the domain an opposing cadherin molecule, or freed from the domain and exposed to solvent. Until now, the physiological relevance of these structures has been controversial. Using conformation specific antibodies I show that Trp2 integrates into the domain fold of its own cadherin molecule in physiological conditions, but that this integration is not stable owing to structural constraints imposed by calcium binding to the cadherin. This raises the possibility that Trp2 could participate in intermolecular interactions during adhesion by inserting into opposing cadherins in what is referred to as the strand exchange model of cadherin adhesion. This model is tested directly by introducing cysteine substitutions into opposing cadherins ...
Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.
Cadherins are transmembrane glycoproteins vital in calcium-dependent cell-cell adhesion during tissue differentiation. Cadherins cluster to form foci of homophilic binding units. A key determinant to the strength of the cadherin-mediated adhesion may be by the juxtamembrane region in cadherins. This region induces clus
Sideridou M, Zakopoulou R, Evangelou K, Liontos M, Kotsinas A, Rampakakis E, Gagos S, Kahata K, Grabusic K, Gkouskou K, Trougakos IP, Kolettas E, Georgakilas AG, Volarevic S, Eliopoulos AG, Zannis-Hadjopoulos M, Moustakas A, Gorgoulis VG J. Cell Biol. 195 (7) 1123-1140 [2011-12-26; online 2011-12-28] E-cadherin (CDH1) loss occurs frequently in carcinogenesis, contributing to invasion and metastasis. We observed that mouse and human epithelial cell lines overexpressing the replication licensing factor Cdc6 underwent phenotypic changes with mesenchymal features and loss of E-cadherin. Analysis in various types of human cancer revealed a strong correlation between increased Cdc6 expression and reduced E-cadherin levels. Prompted by these findings, we discovered that Cdc6 repressed CDH1 transcription by binding to the E-boxes of its promoter, leading to dissociation of the chromosomal insulator CTCF, displacement of the histone variant H2A.Z, and promoter heterochromatinization. Mutational analysis ...
TY - JOUR. T1 - Similarities between heterophilic and homophilic cadherin adhesion. AU - Prakasam, A. K.. AU - Maruthamuthu, V.. AU - Leckband, D. E.. PY - 2006/10/17. Y1 - 2006/10/17. N2 - The mechanism that drives the segregation of cells into tissue-specific subpopulations during development is largely attributed to differences in intercellular adhesion. This process requires the cadherin family of calcium-dependent glycoproteins. A widely held view is that protein-level discrimination between different cadherins on cell surfaces drives this sorting process. Despite this postulated molecular selectivity, adhesion selectivity has not been quantitatively verified at the protein level. In this work, molecular force measurements and bead aggregation assays tested whether differences in cadherin bond strengths could account for cell sorting in vivo and in vitro. Studies were conducted with chicken N-cadherin, canine E-cadherin, and Xenopus C-cadherin. Both qualitative bead aggregation and ...
TY - JOUR. T1 - Expression of cadherins and catenins in paired tumor and non-neoplastic primary prostate cultures and corresponding prostatectomy specimens. AU - Wang, J.. AU - Krill, D.. AU - Torbenson, Michael. AU - Wang, Q.. AU - Bisceglia, M.. AU - Stoner, J.. AU - Thomas, A.. AU - DeFlavia, P.. AU - Dhir, R.. AU - Becich, M. J.. PY - 2000/1/1. Y1 - 2000/1/1. N2 - Cadherins are a family of transmembrane proteins that play a crucial role in cell differentiation, cell migration, and intercellular adhesion. Cadherins are associated with catenins through their highly conserved cytoplasmic domain. Down-regulation of E-cadherin protein has been shown in various human cancers. This study examined the expression of cadherins and associated catenins at the mRNA level. Paired tumor and non-neoplastic primary prostate cultures were obtained from surgical specimens. Quantitative multiplex fluorescence reverse transcriptase-polymerase chain reaction (QMF RT-PCR) and quantitative analysis were performed ...
We show in this paper that this can indeed occur, in a cell culture system in which Wg signaling can be controlled and its response be measured over time. We found two contrasting effects: Wg initially lowers the amount of the cadherin-catenin complex at cell-cell contacts, most probably by reducing the Arm pool interacting with E-cadherin, but later, Wg signaling leads to elevated DE-cadherin transcription. This later increase in DE cadherin may titrate the pool of Arm available for Wg signaling and therefore attenuate the transcriptional response to Wg. We have shown by metabolic labeling experiments that the reduction in E-cadherin levels was caused by a posttranscriptional mechanism that affected the stability of the E-cadherin protein. Although levels of E-cadherin precursors were similar in the absence or presence of Wg signaling, very little mature E-cadherin was detectable in cells with an activated Wg pathway, indicating that the majority of E-cadherin was either degraded before arrival ...
E-Cadherin is calcium-dependent cell adhesion molecule encoded by CDH1 gene at chromosome 16q22.1. Ecadherin regulates cell-cell adhesions and controls mobility and proli..
E-cadherin (epithelial cadherin, CDH1, OMIM# 192090) is a member of the cadherin family of adhesion molecules, which are transmembrane glycoproteins mediating calcium-dependent cell-cell adhesion1. Germline mutations in the CDH1 gene have been demonstrated to underlie in diffuse gastric cancer (DGC) in various ethnic backgrounds 2, 3, 4. CDH1 germ line mutations have also been identified in a small portion of early onset DGC patients without a family history 5, 6, 12. Associations between CDH1 germ line mutations and both lobular breast cancer and signet ring carcinoma of the colon have been reported in DGC families 7, 8, 9. DGC is a highly penetrant autosomal dominant disorder that has been reported to occur in many ethnicities. The offspring of an affected individual has a 50% risk of also being affected. The estimated cumulative risk of gastric cancer by age 80 years is 67% (95% CI: 39-99) for men and 83% (95% CI: 58-99) for women10. Women also have a 39% risk for lobular breast cancer10. ...
Our laboratory is interested in understanding fundamental mechanisms of transcription and RNA splicing in the nervous system, and how these mechanisms bear on neuronal connectivity and neurodegenerative diseases. Interest in neuronal connectivity arose from our discovery of a remarkable organization of a large cluster of genes encoding cell surface cadherin-like proteins called protocadherins. This unusual gene organization leads to the generation of enormous individual cell surface diversity at the synapse through a mechanism that involves stochastic promoter choice and alternative RNA splicing. We are studying the detailed mechanisms of promoter choice, and are using gene knock out methods to investigate the function of protocadherins. We are also using embryonic stem cell differentiation and deep sequencing methods to study transcription, RNA splicing, protein-RNA interactions, and microRNAs in ALS disease models. This involves studies of SOD1, FUS and TDP43 mouse models, and human patient ...
Our results show that NFPC and TAF1 are expressed in RGCs and that inhibition of either NFPC or TAF1 function in vivo severely impairs axon and dendrite extension. These findings, together with recent reports showing that γ-protocadherins regulate synaptic development in spinal cord neurons (Weiner et al., 2005), and OL-protocadherin controls striatal axon elongation in the ventral telencephalon (Uemura et al., 2007), implicate protocadherins as general players in axonogenesis and dendritogenesis.. Although it is apparent that NFPC plays an integral role in RGC axon and dendrite elongation, its precise function at the level of the growth cone is unclear. NFPC was first identified as a regulator of embryonic ectodermal formation in Xenopus. In vivo inhibition of NFPC with NFΔE resulted in a failure of the nascent ectodermal layers to juxtapose, indicating a failure of adhesion in those NFΔE-expressing regions (Bradley et al., 1998). NFPC has also been implicated in the regulation of neural ...
Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells. Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7.
Title:Cadherins: The Superfamily Critically Involved in Breast Cancer. VOLUME: 22 ISSUE: 5. Author(s):Maeirah Afzal Ashaie and Ezharul Hoque Chowdhury. Affiliation:Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia.. Keywords:Breast cancer, cell adhesion, cadherins, CDH1, CDH2, epigenetic silencing, EMT, tumor repressor, transcriptional factors, signaling pathways.. Abstract:Breast cancer, one of the leading causes of mortality and morbidity among females, is regulated in part by diverse classes of adhesion molecules one of which is known as cadherins. Located at adherens junctions, the members of this superfamily are responsible for upholding proper cell-cell adhesion. Cadherins possess diverse structures and functions and any alteration in their structures or functions causes impeding of normal mammary cells development and maintenance, thus leading to breast malignancy. E-, N-, P-, VE-, Proto-, desmosomal and FAT cadherins have been found to regulate breast cancer ...
Epithelial (E)-cadherin and its associated cytoplasmic proteins (alpha-, beta-, and gamma-catenins) are important mediators of epithelial cell-cell adhesion and intracellular signaling. Much evidence exists suggesting a tumor/invasion suppressor role for E-cadherin, and loss of expression, as well as mutations, has been described in a number of epithelial cancers. To investigate whether E-cadherin gene (CDH1) mutations occur in colorectal cancer, we screened 49 human colon carcinoma cell lines from 43 patients by single-strand conformation polymorphism (SSCP) analysis and direct sequencing. In addition to silent changes, polymorphisms, and intronic variants in a number of the cell lines, we detected frameshift single-base deletions in repeat regions of exon 3 (codons 120 and 126) causing premature truncations at codon 216 in four replication-error-positive (RER+) cell lines (LS174T, HCT116, GP2d, and GP5d) derived from 3 patients. In LS174T such a mutation inevitably contributes to its lack of E
E-cadherin interacts with other E-cadherin molecules on neighboring cells to form cell-cell adhesions. E-cadherin that is not involved in these trans interactions is removed from the cell surface and replaced with newly synthesized molecules to maintain dynamic adhesions. Now, Izumi et al. (page 237) show that E-cadherins that are involved in trans interactions are excused from this endocytosis by small GTPases. Disruption of this system may free cells for migration.. By reconstituting endocytosis in membrane bilayers, the group shows that clathrin-dependent endocytosis removes E-cadherin that is not interacting in trans with other E-cadherins. E-cadherins engaged in trans interactions, however, activated Rac and Cdc42, which blocked their internalization. So far it is unclear how the trans interactions activate the G proteins.. The endocytic block is enhanced by IQGAP1, an effector of Rac and Cdc42. IQGAP1 cross-links actin filaments into bundles, and the group shows that F-actin is needed to ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the cadherin superfamily whose members encode calcium-dependent cell-cell adhesion molecules. The encoded protein has a signal peptide, 27 cadherin repeat domains and a unique cytoplasmic region. This particular cadherin family member is expressed in fibroblasts but not in melanocytes or keratinocytes. The cell-cell adhesion of fibroblasts is thought to be necessary for wound healing. [provided by RefSeq, Jul 2008 ...
Known proteins from the cell-adhesion protein E-cadherin include proteins and catenins involved with signaling trafficking and actin organization. catenins and almost 40 others that were previously reported to influence cadherin function. Many others could be rationalized as novel candidates for regulating the adherens junction Isovitexin cytoskeleton trafficking or signaling. We further characterized lipoma desired partner (LPP) which is present at both cell contacts and focal adhesions. Knockdown of LPP shown its requirement for E-cadherin-dependent adhesion and suggested that it plays a role in coordination of the cell-cell and cell-substrate cytoskeletal relationships. The analysis of LPP function demonstrates proof of principle the proteomic analysis of E-cadherin proximal proteins expands the inventory of parts and tools for understanding the function of E-cadherin. proximity ligation assay (PLA); this assay results in the production of a fluorescent transmission when antibodies to two ...
This gene encodes a member of the protocadherin family, and cadherin superfamily, of transmembrane proteins containing cadherin domains. These proteins mediate cell adhesion in neural tissues in the presence of calcium. The encoded protein may be involved in signaling at neuronal synaptic junctions. Sharing a characteristic with other protocadherin genes, this gene has a notably large exon that encodes multiple cadherin domains and a transmembrane region. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Nov 2012 ...
Several events during the normal development of the mammalian neocortex depend on N-cadherin, including the radial migration of immature projection neurons into the cortical plate. Remarkably, radial migration requires the N-cadherin extracellular domain but not N-cadherin-dependent homophilic cell-cell adhesion, suggesting that other N-cadherin-binding proteins may be involved. We used proximity ligation and affinity purification proteomics to identify N-cadherin-binding proteins. Both screens detected MycBP2 and SPRY domain protein Fbxo45, two components of an intracellular E3 ubiquitin ligase. Fbxo45 appears to be secreted by a nonclassical mechanism, not involving a signal peptide and not requiring transport from the endoplasmic reticulum to the Golgi apparatus. Fbxo45 binding requires N-cadherin SPRY motifs that are not involved in cell-cell adhesion. SPRY mutant N-cadherin does not support radial migration in vivo. Radial migration was similarly inhibited when Fbxo45 expression was ...
Cadherins are a family of glycoproteins involved in the Ca2+-dependent cell-cell adhesion mechanism which is detected in most kinds of tissues. Inhibition of the cadherin activity with antibodies induces dissociation of cell layers, indicating a fundamental importance of these molecules in maintaining the multicellular structure. Cadherins are divided into subclasses, including E-, N- and P-cadherins. While all subclasses are similar in molecular weight, Ca2+- and protease-sensitivity, each subclass is characterized by a unique tissue distribution pattern and immunological specificity. Analysis of amino acid sequences deduced from cDNA encoding these molecules showed that they are integral membrane proteins of 723-748 amino acids long and share common sequences; similarity in the sequences between subclasses is in a range of 50-60% when compared within a single animal species. L cells, with very little endogenous cadherin activity, transfected with the cadherin cDNA acquired high ...
Cadherins are a family of glycoproteins involved in the Ca2+-dependent cell-cell adhesion mechanism which is detected in most kinds of tissues. Inhibition of the cadherin activity with antibodies induces dissociation of cell layers, indicating a fundamental importance of these molecules in maintaining the multicellular structure. Cadherins are divided into subclasses, including E-, N- and P-cadherins. While all subclasses are similar in molecular weight, Ca2+- and protease-sensitivity, each subclass is characterized by a unique tissue distribution pattern and immunological specificity. Analysis of amino acid sequences deduced from cDNA encoding these molecules showed that they are integral membrane proteins of 723-748 amino acids long and share common sequences; similarity in the sequences between subclasses is in a range of 50-60% when compared within a single animal species. L cells, with very little endogenous cadherin activity, transfected with the cadherin cDNA acquired high ...
There is increasing evidence supporting DNA virus regulation of the cell adhesion and tumour suppressor protein, E-cadherin. At the6 STF-62247 conveying cells. Upon inhibiting DNMT activity using 5-Aza-2-deoxycytidine, E-cadherin transcription was restored in the presence of HPV16 At the6. The E-cadherin promoter was not directly methylated, however a mutational analysis showed general promoter repression and reduced binding of the transactivators Sp1 and AML1 and the repressor Slug. Manifestation of At the7 with At the6 resulted in a further reduction in surface E-cadherin levels. This is usually the first statement of HPV16 At the6-mediated transcriptional repression of this adhesion molecule and tumour suppressor protein. Introduction Cervical malignancy is usually the second most common malignancy among women worldwide, with over 500,000 new cases being diagnosed annually [1]. The majority of cases of cervical malignancy are a result of contamination with high-risk, oncogenic human ...
The DNA damage repair gene PALB2 is well described as increasing risk of breast and ovarian cancer when mutated. In a sequencing study of hereditary diffuse gastric cancer (HDGC) families, Eleanor Fewings as a part of the Tischkowitz lab, has shown that predicted pathogenic mutations in PALB2 also occur in high risk HDGC families. Mutations in the E-cadherin gene CDH1 greatly impact HDGC risk, however many HDGC families are identified without mutations in this gene. For these families, the choice to undergo risk reducing surgery is based on poorly informed risk calculations. This study named new genetic candidates for HDGC risk including PALB2, ATR, NBN, and RECQL5. Identification of these genes could provide families with HDGC who dont carry CDH1 pathogenic variants with improved information about the risks associated with their disease and allow them to make informed decisions about risk reduction and disease management.. Link: ...
TY - JOUR. T1 - Dysadherin, a cancer-associated cell membrane glycoprotein, down-regulates E-cadherin and promotes metastasis. AU - Ino, Yoshinori. AU - Gotoh, Masahiro. AU - Sakamoto, Michiie. AU - Tsukagoshi, Kiyomi. AU - Hirohashi, Setsuo. PY - 2002/1/8. Y1 - 2002/1/8. N2 - We report the cloning and characterization of a cancer-associated cell membrane glycoprotein recognized by mAb NCC-3G10. The antibody showed strong reactivity to a wide variety of cancer cells, but only to a limited number of normal cells including lymphocytes, endothelial cells, and basal cells of stratified squamous epithelium. The cDNA for the antigen encodes 178 aa, which includes a putative signal sequence, a potential O-glycosylated extracellular domain, a single transmembrane domain, and a short cytoplasmic tail. Transfection of the cDNA into PLC/PRF/5 liver cancer cells resulted in reduced cell-cell adhesiveness, based on both morphology and results of Ca2+-dependent cell aggregation assay. In transfected cells, ...
N-cadherin is the predominant mediator of calcium-dependent adhesion in the nervous system (Takeichi, M. 1988. Development (Camb.). 102: 639-655). Investigations using antibodies to block N-cadherin function (Bixby, J.L., R.L. Pratt, J. Lilien, and L.F. Reichardt. 1987. Proc. Natl. Acad. Sci. USA. 84:2555-2569; Bixby, J.L., J. Lilien, and L.F. Reichardt. 1988. J. Cell Biol. 107:353-362; Tomaselli, K.J., K.N. Neugebauer, J.L. Bixby, J. Lilien, and L.F. Reichardt. 1988. Neuron. 1:33-43) or transfection of the N-cadherin gene into heterologous cell lines (Matsunaga, M., K. Hatta, A. Nagafuchi, and M. Takeichi. 1988. Nature (Lond.). 334:62-64) have provided evidence that N-cadherin, alone or in combination with other molecules, can participate in the induction of neurite extension. We have developed an affinity purification procedure for the isolation of whole N-cadherin from chick brain and have used the isolated protein as a substrate for neurite outgrowth. N-cadherin promotes the rapid extension ...
Cadherins are calcium-dependent, cell surface glycoproteins involved in cell-cell adhesion. To function in cell-cell adhesion, the transmembrane cadherin molecule must be associated with the cytoskeleton via cytoplasmic proteins known as catenins. Three catenins, alpha-catenin, beta-catenin, and gamma-catenin (also known as plakoglobin), have been identified. The domain of the cadherin molecule important for its interaction with the catenins has been mapped to the COOH-terminal 70 amino acids, but less is known about regions of the catenins that allow them to associate with one another or with the cadherin molecule. In this study we have transfected carboxyl-terminal deletions of plakoglobin into the human fibrosarcoma HT-1080 and used immunofluorescence localization and co-immunoprecipitation to map the regions of plakoglobin that allow it to associate with N-cadherin and with alpha-catenin. Plakoglobin is an armadillo family member containing 13 weakly similar internal repeats. These data show ...
Cell-surface markers of EMT. A change in expression of E-cadherin is the prototypical epithelial cell marker of EMT. E-cadherin is expressed in epithelial cells, and its expression is decreased during EMT in embryonic development, tissue fibrosis, and cancer (65). Moreover, loss of E-cadherin function promotes EMT (4, 66). In recent years, changes in the level of expression of different cadherins, so-called cadherin switches, have been increasingly used to monitor EMT. Indeed, the cadherin switch from E-cadherin to N-cadherin, which is expressed in mesenchymal cells, fibroblasts, cancer cells, and neural tissue, has often been used to monitor the progress of EMT during embryonic development and cancer progression. In addition, because OB-cadherin is a more definitive marker for activated fibroblasts, an E-cadherin-OB-cadherin switch is of interest for type 2 EMT associated with fibrogenesis (67). EMT is associated classically with a relocation of cells from a basement membrane microenvironment ...
Clone REA199 recognizes CD144 (VE-Cadherin), a 120 KDa type II cadherin. Cadherins are cell adhesion molecules and mediate Ca2+ dependent homophilic interactions. CD144 contains five extracellular cadherin (EC) domains and like other cadherins can interact directly via its C-terminus with cytoplasmic proteins such as β-catenin, plaktoglobin, and p120. Plaktoglobin und β-catenin bind to α-catenin, which in turn interacts with several actin-binding proteins, α-actinin, ajuba, zonula occludens-1 (ZO-1). Further indirect interactions of CD144 with partners such as SHP-2, VEGFR-2, Csk, and PAR-3, 6 allows CD144 to not only regulate the stability and strength of cell adhesion but also to serve functions such as sensing of shear forces, anti-proliferative, and anti-apoptotic effects. Additional information: Clone REA199 displays negligible binding to Fc receptors. - Schweiz
Clone REA199 recognizes CD144 (VE-Cadherin), a 120 KDa type II cadherin. Cadherins are cell adhesion molecules and mediate Ca2+ dependent homophilic interactions. CD144 contains five extracellular cadherin (EC) domains and like other cadherins can interact directly via its C-terminus with cytoplasmic proteins such as β-catenin, plaktoglobin, and p120. Plaktoglobin und β-catenin bind to α-catenin, which in turn interacts with several actin-binding proteins, α-actinin, ajuba, zonula occludens-1 (ZO-1). Further indirect interactions of CD144 with partners such as SHP-2, VEGFR-2, Csk, and PAR-3, 6 allows CD144 to not only regulate the stability and strength of cell adhesion but also to serve functions such as sensing of shear forces, anti-proliferative, and anti-apoptotic effects. Additional information: Clone REA199 displays negligible binding to Fc receptors. - Ireland
Cadherin 2, also known as N-cadherin, is a member of the cadherin superfamily of predominantly Ca2+-dependent cell surface adhesion proteins.30 In the heart, cadherin 2 is located at the intercalated disc, a complex and highly organized intercellular structure that ensures structural integrity and functional synchronization across the myocardium through the tight electromechanical coupling of cardiomyocytes.30,31 In the intercalated disc, intercellular communication and adhesion are achieved through 3 main junctional structures forming functional zones, the gap junctions, the fascia adherens junctions, and the desmosomes, with the latter 2 being the main contributors to cell-cell adhesion.30-32 In desmosomes, desmosomal cadherins (desmocollin and desmoglein) are mainly anchored to the intermediate filaments of the cytoskeleton through many intracellular protein partners, whereas in fascia adherens junctions, the classical cadherin, N-cadherin, is primarily anchored to the actin microfilaments of ...
This gene is a member of the protocadherin beta gene cluster, one of three related gene clusters tandemly linked on chromosome five. The gene clusters demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The beta cluster contains 16 genes and 3 pseudogenes, each encoding 6 extracellular cadherin domains and a cytoplasmic tail that deviates from others in the cadherin superfamily. The extracellular domains interact in a homophilic manner to specify differential cell-cell connections. Unlike the alpha and gamma clusters, the transcripts from these genes are made up of only one large exon, not sharing common 3 exons as expected. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins. Their specific functions are unknown but they most likely play a critical role in the establishment and function of specific cell-cell neural connections ...
Cadherins play an important role in morphogenesis and have recently been implicated in the regulation of cell proliferation, however the mechanisms by which they function are poorly understood. In the vertebrate CNS, loss of ,italic,N-cadherin (N-cad),,/, results in impaired neuroepithelial integrity. Zebrafish ,italic,N-cad,,/, null mutants also exhibit a transient increase in neurons and in cell proliferation in the neural tube. Here, we investigate the cellular and molecular basis for this phenotype, using multiple ,italic,N-cad,,/, alleles with distinct molecular properties. We confirm that cell proliferation is enhanced in ,italic,N-cad,,/, mutants, but contrary to previous findings, we observe that the increase is sustained over multiple stages of development. At the cellular level, loss of ,italic,N-cad,,/, results in a shorter cell cycle. Furthermore, we demonstrate that hyperproliferation is not linked to abnormal beta-catenin localization, suggesting that Wnt signaling is not ...
Cadherins play an important role in morphogenesis and have recently been implicated in the regulation of cell proliferation, however the mechanisms by which they function are poorly understood. In the vertebrate CNS, loss of ,italic,N-cadherin (N-cad),,/, results in impaired neuroepithelial integrity. Zebrafish ,italic,N-cad,,/, null mutants also exhibit a transient increase in neurons and in cell proliferation in the neural tube. Here, we investigate the cellular and molecular basis for this phenotype, using multiple ,italic,N-cad,,/, alleles with distinct molecular properties. We confirm that cell proliferation is enhanced in ,italic,N-cad,,/, mutants, but contrary to previous findings, we observe that the increase is sustained over multiple stages of development. At the cellular level, loss of ,italic,N-cad,,/, results in a shorter cell cycle. Furthermore, we demonstrate that hyperproliferation is not linked to abnormal beta-catenin localization, suggesting that Wnt signaling is not ...
Cadherin like 23 (or Cadherin 23) is, like other members of the cadherin family, a calcium-dependent cell adhesion glycoprotein that preferentially…
Sigma-Aldrich offers abstracts and full-text articles by [Maria Sideridou, Roubini Zakopoulou, Konstantinos Evangelou, Michalis Liontos, Athanassios Kotsinas, Emmanouil Rampakakis, Sarantis Gagos, Kaoru Kahata, Kristina Grabusic, Kalliopi Gkouskou, Ioannis P Trougakos, Evangelos Kolettas, Alexandros G Georgakilas, Sinisa Volarevic, Aristides G Eliopoulos, Maria Zannis-Hadjopoulos, Aristidis Moustakas, Vassilis G Gorgoulis].