A5031653711- Protein Kinase Regulation and GTPase Signaling
- Axon Guidance and Neuronal Signaling
- Cellular transport and secretion
- Cellular Mechanics and Interactions
- Sarcoma Diagnosis and Treatment
- Microtubule and mitosis dynamics
- Protein Tyrosine Phosphatases
- Glycosylation and Glycoproteins Research
- Metabolism, Diabetes, and Cancer
- Receptor Mechanisms and Signaling
- Ubiquitin and proteasome pathways
- Signaling Pathways in Disease
- PI3K/AKT/mTOR signaling in cancer
- Cell Adhesion Molecules Research
- Hippo pathway signaling and YAP/TAZ
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related molecular mechanisms research
- Neurogenesis and neuroplasticity mechanisms
- Cancer-related Molecular Pathways
- Virus-based gene therapy research
- RNA Research and Splicing
- Wnt/β-catenin signaling in development and cancer
- RNA and protein synthesis mechanisms
- Retinal Development and Disorders
- Biochemical Analysis and Sensing Techniques
Centre de Recherche en Biologie cellulaire de Montpellier
2005-2024
Centre National de la Recherche Scientifique
2010-2024
Université de Montpellier
2008-2024
Dynamique du noyau
2014
Inserm
1985-1997
Hôpital Pasteur
1985-1997
Dana-Farber Cancer Institute
1995-1996
Collège de France
1992
Centre Méditerranéen de Médecine Moléculaire
1990
Institut de Biologie Valrose
1985
rho-like GTP binding proteins play an essential role in regulating cell growth and actin polymerization. These molecular switches are positively regulated by guanine nucleotide exchange factors (GEFs) that promote the of GDP for GTP. Using interaction-trap assay to identify candidate bind cytoplasmic region LAR transmembrane protein tyrosine phosphatase (PT-Pase), we isolated a cDNA encoding 2861-amino acid termed Trio contains three enzyme domains: two functional GEF domains...
The chemotropic guidance cue netrin-1 promotes neurite outgrowth through its receptor Deleted in Colorectal Cancer (DCC) via activation of Rac1. guanine nucleotide exchange factor (GEF) linking netrin-1/DCC to Rac1 has not yet been identified. Here, we show that the RhoGEF Trio mediates signaling. We found interacts with DCC mouse embryonic brains and netrin-1-induced brain is impaired absence Trio. Trio−/− cortical neurons fail extend neurites response netrin-1, while they are able respond...
Epithelial invagination is a common feature of embryogenesis. An example morphogenesis occurs during development the early eye when lens placode forms pit. This accompanied by columnar-to-conical cell shape change (apical constriction or AC) and known to be dependent on cytoskeletal protein Shroom3. Because Shroom3-induced AC can Rock1/2 dependent, we hypothesized that invagination, RhoA, Rock RhoA guanine nucleotide exchange factor (RhoA-GEF) would also required. In this study, show...
The Rho-guanine nucleotide exchange factor (RhoGEF) TRIO acts as a key regulator of neuronal migration, axonal outgrowth, axon guidance, and synaptogenesis by activating the GTPase RAC1 modulating actin cytoskeleton remodeling. Pathogenic variants in are associated with neurodevelopmental diseases, including intellectual disability (ID) autism spectrum disorders (ASD). Here, we report largest international cohort 24 individuals confirmed pathogenic missense or nonsense TRIO. mutations spread...
Rho GTPases regulate the morphology of cells stimulated by extracellular ligands. Their activation is controlled guanine exchange factors (GEF) that catalyze their binding to GTP. The multidomain Trio protein represents an emerging class &Rgr; regulators contain two GEF domains distinct specificities. We report here characterization signaling pathways activated N-terminal domain (TrioD1). In fibroblasts, TrioD1 triggers formation particular cell structures, similar those elicited RhoG, a...
Cadherins are transmembrane glycoproteins that mediate Ca(2+)-dependent homophilic cell-cell adhesion and play crucial role during skeletal myogenesis. M-cadherin is required for myoblast fusion into myotubes, but its mechanisms of action remain unknown. The goal this study was to cast some light on the nature M-cadherin-mediated signals involved in myotubes. We found Rac1 GTPase activity increased at time it process. Moreover, we showed M-cadherin-dependent activates demonstrated formation...
Neurodevelopmental disorders have challenged clinical genetics for decades, with over 700 genes implicated and many whose function remains unknown. The application of whole-exome sequencing is proving pivotal in closing the genotype/phenotype gap through discovery new variants that help to unravel pathogenic mechanisms driving neuropathogenesis. One such includes TRIO, a gene recently neurodevelopmental delay. Trio Dbl family guanine nucleotide exchange factor (GEF) major regulator neuronal...
The transcription factor Elk-1 is a nuclear target of mitogen-activated protein kinases and regulates immediate early gene activation by extracellular signals. We show that also conjugated to SUMO on either lysines 230, 249, or 254. Mutation all three sites necessary fully block SUMOylation in vitro vivo. This mutant, Elk-1(3R), shuttles more rapidly nuclei Balb/C cells fused transfected HeLa cells. Coexpression SUMO-1 -2 strongly reduces shuttling without affecting indicating retention...
Chinese hamster ovary transfectants that express insulin receptors in which tyrosine residues 1162 and 1163 were replaced by phenylalanine exhibit a total inhibition of the insulin-mediated kinase activity toward exogenous substrates [histone, casein, poly(Glu/Tyr)]; this latter is associated with hypersensitivity reported for promoting 2-deoxyglucose uptake. We now present evidence twin tyrosines also control stimulation glycogen synthesis. Surprisingly, type transfectant as hypersensitive...
Neurite extension depends on extracellular signals that lead to changes in gene expression and rearrangement of the actin cytoskeleton. A factor might orchestrate these signalling pathways with cytoskeletal elements is integral membrane protein Kidins220/ARMS, a downstream target neurotrophins. Here, we identified Trio, RhoGEF for Rac1, RhoG RhoA, which involved neurite outgrowth axon guidance, as binding partner Kidins220. This interaction direct occurs between N-terminus Trio ankyrin...
The chemotropic guidance cue netrin-1 mediates attraction of migrating axons during central nervous system development through the receptor Deleted in Colorectal Cancer (DCC). Downstream netrin-1, activated Rho GTPases Rac1 and Cdc42 induce cytoskeletal rearrangements within growth cone. guanine nucleotide exchange factor (GEF) Trio is essential for activation downstream netrin-1/DCC, but molecular mechanisms governing activity remain elusive. Here, we demonstrate that phosphorylated by Src...
Abstract Purpose: Despite various differences, nontranslocation-related sarcomas (e.g., comprising undifferentiated pleomorphic sarcoma, leiomyosarcoma, myxofibrosarcoma) are unified by their complex genetics. Extensive analysis of the tumor genome using molecular cytogenetic approaches showed many chromosomal gains, losses, and translocations per cell. Genomic quantitative alterations expression variations have been extensively studied adapted high-throughput approaches, yet still remained...
Insulin receptor (IR) is a glycoprotein possessing N-linked oligosaccharide side chains on both alpha and beta subunits. The present study focuses for the first time potential contribution of oligosaccharides subunit in processing, structure, function insulin receptor. To investigate this point, mutant (IR N1234) was obtained by stable transfection into Chinese hamster ovary cells an IR cDNA modified site-directed mutagenesis four N-glycosylation sites (Asn-X-Ser/Thr) subunit. mutated...
The Rho–guanine nucleotide exchange factors (Rho–GEFs) remodel the actin cytoskeleton via their Rho–GTPase targets and affect numerous physiological processes such as transformation cell motility. They are therefore attractive to design specific inhibitors that may have therapeutic applications. Trio contains two Rho–GEF domains, GEFD1 GEFD2, which activate Rac RhoA pathways, respectively. Here we used a genetic screen in yeast select vivo peptides coupled thioredoxin, called aptamers, could...
Addition of insulin to wheat-germ-lectin-purified glycoproteins derived from rat hepatocytes or rabbit brown adipose tissue results in the increased phosphorylation a Mr-110 000 protein. This naturally occurring glycoprotein appears as monomeric structure and is not part receptor itself, since it immunoprecipitated by highly specific antibodies receptor. Phosphorylation protein autophosphorylation beta-subunit (Mr 95 000) are stimulated remarkably similar dose-dependent fasion, with...