A TAT–DEF–Elk-1 Peptide Regulates the Cytonuclear Trafficking of Elk-1 and Controls Cytoskeleton Dynamics
| Autor: | Frédéric Bernard, Vincent Kappes, Vincent Pascoli, Pierre Trifilieff, Christiane Pagès, Peter Vanhoutte, Jocelyne Caboche, Jeremie Lavaur |
|---|---|
| Přispěvatelé: | Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neurosciences cognitives (NC), Université Sciences et Technologies - Bordeaux 1 (UB)-Centre National de la Recherche Scientifique (CNRS), Transduction du Signal et Plasticite Dans Le Systeme Nerveux, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Division of Neurobiology, Laboratory of Molecular Biology [Cambridge], Medical Research Council-Medical Research Council, Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2007 |
| Předmět: |
Male
MAPK/ERK pathway MESH: Dopamine Uptake Inhibitors animal diseases MESH: Neurons MESH: Corpus Striatum Mice fluids and secretions 0302 clinical medicine Cocaine Dopamine Uptake Inhibitors Serine MESH: Animals Enzyme Inhibitors Phosphorylation Cells Cultured Cytoskeleton ComputingMilieux_MISCELLANEOUS Neurons 0303 health sciences MESH: Peptides Kinase General Neuroscience Cell Differentiation Articles MESH: Glutamic Acid Cell biology Protein Transport MESH: Enzyme Inhibitors Mitogen-activated protein kinase [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Mitogen-Activated Protein Kinases Subcellular Fractions MESH: Cells Cultured MESH: Cell Differentiation MESH: Protein Transport Glutamic Acid Biology Transfection CREB 03 medical and health sciences MESH: Cocaine MESH: Mice Inbred C57BL Serum response factor MESH: Cytoskeleton Animals MESH: ets-Domain Protein Elk-1 MESH: Serine Protein kinase A MESH: Mice Transcription factor ets-Domain Protein Elk-1 030304 developmental biology MESH: Phosphorylation MESH: Transfection [SCCO.NEUR]Cognitive science/Neuroscience MESH: Embryo Mammalian Embryo Mammalian MESH: Mitogen-Activated Protein Kinases Corpus Striatum MESH: Male Mice Inbred C57BL MESH: Subcellular Fractions biology.protein Peptides 030217 neurology & neurosurgery |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience, 2007, 27 (52), pp.14448-14458. ⟨10.1523/JNEUROSCI.2279-07.2007⟩ Journal of Neuroscience, Society for Neuroscience, 2007, 27 (52), pp.14448-58. ⟨10.1523/JNEUROSCI.2279-07.2007⟩ Journal of Neuroscience, Society for Neuroscience, 2007, 27 (52), pp.14448-14458. ⟨10.1523/JNEUROSCI.2279-07.2007⟩ Journal of Neuroscience, 2007, 27 (52), pp.14448-58. ⟨10.1523/JNEUROSCI.2279-07.2007⟩ |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | The transcription factor Elk-1 plays a key role in cell differentiation, proliferation and apoptosis. This role is thought to arise from its phosphorylation by activated extracellular signal-regulated kinases (ERKs), a critical posttranslational event for the transcriptional activity of the ternary complex composed of Elk-1 and a dimer of serum response factor (SRF) at the serum response element (SRE) regulatory site of transcription. In addition to its nuclear localization, Elk-1 is found in the dendrites and soma of neuronal cells and recent evidence implicate a cytoplasmic proapoptotic function of Elk-1, via its association with the mitochondrial permeability transition pore complex. Thus, the nuclear versus cytoplasmic localization of Elk-1 seems to be crucial for its biological function. In this study we show that the excitatory neurotransmitter, glutamate, induces an ERK-dependent Elk-1 activation and nuclear relocalization. We demonstrate that Elk-1 phosphorylation on Ser383/389 has a dual function and triggers both Elk-1 nuclear translocation and SRE-dependent gene expression. Mutating these sites into inactive residues or using a synthetic penetrating peptide (TAT–DEF–Elk-1), which specifically interferes with the DEF docking domain of Elk-1, prevents Elk-1 nuclear translocation without interfering with ERK nor MSK1 (mitogen- and stress-activated protein kinase 1), a CREB kinase downstream from ERK- activation. This results in a differential regulation of glutamate-induced IEG regulation when compared with classical inhibitors of the ERK pathway. Using the TAT–DEF–Elk-1 peptide or the dominant-negative version of Elk-1, we show that Elk-1 phosphorylation controls dendritic elongation, SRF and Actin expression levels as well as cytoskeleton dynamics. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|