A5022928809- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Cardiovascular Effects of Exercise
- Cardiac Valve Diseases and Treatments
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- Connective tissue disorders research
- CRISPR and Genetic Engineering
- Cardiomyopathy and Myosin Studies
- Tissue Engineering and Regenerative Medicine
- Cardiac electrophysiology and arrhythmias
- Congenital heart defects research
- Animal Genetics and Reproduction
- Ubiquitin and proteasome pathways
- dental development and anomalies
- 3D Printing in Biomedical Research
- Sports injuries and prevention
- Cancer-related Molecular Pathways
- Hippo pathway signaling and YAP/TAZ
- Cell Adhesion Molecules Research
- Protein Kinase Regulation and GTPase Signaling
- PI3K/AKT/mTOR signaling in cancer
- Cellular Mechanics and Interactions
- Polyamine Metabolism and Applications
- Endoplasmic Reticulum Stress and Disease
Ghent University
2016-2025
Ghent University Hospital
1997-2025
VIB-UGent Center for Inflammation Research
2014-2021
Vlaams Instituut voor Biotechnologie
2000-2020
University of Padua
2014
MRC Laboratory for Molecular Cell Biology
2009
Max Planck Society
2005
MRC Laboratory of Molecular Biology
1995
Îndirect evidence suggests that p120-catenin (p120) can both positively and negatively affect cadherin adhesiveness. Here we show the p120 gene is mutated in SW48 cells, adhesion system impaired as a direct consequence of insufficiency. Restoring normal levels caused striking reversion from poorly differentiated to cobblestone-like epithelial morphology, indicating crucial role for reactivation E-cadherin function. The rescue efficiency was enhanced by increased p120, reduced presence...
AimsArrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of juvenile sudden death and characterized by fibro-fatty replacement the ventricle.Mutations in several genes encoding desmosomal proteins have been identified ARVC.We speculated that aT-catenin, encoded CTNNA3, might also carry mutations ARVC patients.Alpha-T-catenin binds plakophilins this binding contributes to formation area composita, which strengthens cell-cell adhesion contractile cardiomyocytes. Methods...
The positioning of neurons in the cerebral cortex is crucial importance for its function as highlighted by severe consequences migrational disorders patients. Here we show that genetic deletion small GTPase RhoA developing results two disorders: subcortical band heterotopia (SBH), a heterotopic underlying normotopic cortex, and cobblestone lissencephaly, which protrude beyond layer I at pial surface brain. Surprisingly, RhoA(-/-) migrated normally when transplanted into wild-type whereas...
RhoA is a small guanosine-5'-triphosphatase (GTPase) suggested to be essential for cytokinesis, stress fiber formation, and epithelial cell-cell contacts. In skin, loss of was underlie pemphigus skin blistering. To analyze function in vivo, we generated mice with keratinocyte-restricted deletion the gene. Despite severe reduction cofilin myosin light chain (MLC) phosphorylation, these showed normal development. Primary RhoA-null keratinocytes, however, displayed an increased percentage...
Cdc42 is a small GTPase involved in the regulation of cytoskeleton and cell polarity. To test whether has an essential role formation filopodia or directed migration, we generated Cdc42-deficient fibroblastoid cells by conditional gene inactivation. We report here that loss did not affect filopodium lamellipodium had no significant influence on speed migration nor mitosis. displayed more elongated shape reduced area. Furthermore, directionality during reorientation Golgi apparatus into...
We recently established the critical role of lipid phosphatase activity PTEN tumor suppressor in stabilizing cell-cell contacts and suppressing invasiveness. To delineate effector systems involved, we investigated interaction with E-cadherin junctional complexes kidney colonic epithelial cell lines. p85 regulatory subunit phosphatidylinositol 3-OH kinase (PI3K) co-immunoprecipitated catenins. By using a yeast two-hybrid assay, demonstrated that interacted indirectly beta-catenin by binding...
The Armadillo protein p120 ctn associates with the cytoplasmic domain of cadherins and accumulates at cell–cell junctions. Particular proteins such as β-catenin plakophilins show a partly nuclear location, suggesting gene-regulatory activities. For different human E-cadherin-negative carcinoma cancer cell lines we found expression endogenous in nucleus. Expression E-cadherin directed out Previously, reported that gene might encode up to 32 isoforms products alternative splicing....
Alpha-catenins play key functional roles in cadherin-catenin cell-cell adhesion complexes. We previously reported on alphaT-catenin, a novel member of the alpha-catenin protein family. alphaT-catenin is expressed predominantly cardiomyocytes, where it colocalizes with alphaE-catenin at intercalated discs. Whether alphaT- and have specific or synergistic functions remains unknown. In this study we used yeast two-hybrid approach to identify alphaT-catenin. An interaction between plakophilins...
It is generally accepted that the intercalated disc (ICD) required for mechano-electrical coupling in heart consists of three distinct junctional complexes: adherens junctions, desmosomes and gap junctions. However, recent morphological molecular data indicate a mixing desmosomal components, resulting 'hybrid adhering junction' or 'area composita'. The α-catenin family member αT-catenin, part N-cadherin-catenin adhesion complex heart, only interacts with protein plakophilin-2 (PKP2). Thus,...
We report on a novel Armadillo-like protein, termed plakophilin-3. The human which is encoded by 2.8 kb messenger RNA, has predicted molecular mass of 87 kDa. protein comprises 10 repeats, preceded an amino-terminal region 293 amino acid residues and followed short carboxy-terminal 27 residues. Plakophilin-3 classified as member the p120(ctn)/plakophilin subfamily Armadillo proteins based number organization repeats its high sequence similarity to other members this family. CLUSTAL W...
Cadherins are major cell-cell adhesion proteins whose cytoplasmic domains bind to catenin proteins. Strong intercellular depends on linkage of the cadherin/catenin complex actin cytoskeleton via α-catenin. To date, it is not clear how different cell types achieve variable strength clearly needed in a multicellular organism. Here, we report cloning and molecular characterization αT(testis)-catenin, novel human cDNA encoding protein with homology both αE(epithelial)-catenin αN(neural)-catenin....
To analyze the implication of PTEN in control tumor cell invasiveness, canine kidney epithelial lines MDCKras-f and MDCKts-src, expressing activated Ras a temperature-sensitive v-Src tyrosine kinase, respectively, were transfected with expression vectors. Likewise, human PTEN-defective glioblastoma U87MG U373MG, melanoma line FM-45, prostate carcinoma PC-3 transfected. We demonstrate that ectopic wild-type MDCKts-src cells, but not mutants deficient either lipid or both protein phosphatase...
Background & Aims: The Rho small guanosine triphosphatase Cdc42 is critical for diverse cellular functions, including regulation of actin organization, cell polarity, intracellular membrane trafficking, transcription, cell-cycle progression, and transformation. This implies that might be required liver function. Methods: Mice in which was ablated hepatocytes bile duct cells were generated by Cre-loxP technology. Livers examined histologic, immunohistochemical, ultrastructural, serum analysis...
The regulation of adherens junctions (AJs) is critical for multiple events during CNS development, including the formation and maintenance neuroepithelium. We have addressed role small GTPase RhoA in developing mouse nervous system using tissue-specific conditional gene ablation. show that, spinal cord neuroepithelium, essential to localize N-cadherin β-catenin AJs maintain apical–basal polarity neural progenitor cells. Ablation caused loss severe abnormalities organization cells within...
The α-catenin molecule links E-cadherin/ β-catenin or E-cadherin/plakoglobin complexes to the actin cytoskeleton. We studied several invasive human colon carcinoma cell lines lacking α-catenin. They showed a solitary and rounded morphotype that correlated with increased invasiveness. These round variants acquired more normal epithelial phenotype upon transfection an expression plasmid, but also treatment protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Video...
E-cadherin is critical for the maintenance of tissue architecture and a major component adherens junctions. Its role in tumour development well established, with many human carcinomas exhibiting loss at invasive front. In carcinomas, mechanisms leading to remains elusive. Here, we hypothesize that protein quality control play key regulation. As cell model system, used CHO cells stably expressing germline missense mutations R749W E757K, which are associated hereditary diffuse gastric cancer....
H eart tissue is subjected to high mechanical stress.Different junctional complexes exist within the intercalated disc (ID) at site of end-to-end contacts between cardiomyocytes.These junctions are essential for adhesive integrity, morphogenesis, differentiation, and maintenance cardiac tissue.Recent findings molecular interactions among intercellular adhesion molecules, gap junctions, voltage-gated sodium channel complex suggest that IDs should be considered an organelle in which...