HIV-1 Tat Enters T Cells Using Coated Pits before Translocating from Acidified Endosomes and Eliciting Biological Responses
| Autor: | Nadir Bettache, Anne Bonhoure, Agnès Vendeville, Philippe Montcourrier, Fabienne Rayne, Bruno Beaumelle |
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| Přispěvatelé: | Beaumelle, Bruno, Institut universitaire de formation des maîtres - Montpellier (IUFM Montpellier), Université Montpellier 2 - Sciences et Techniques (UM2), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherches de biochimie macromoléculaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-IFR122-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé (CPBS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Centre National de la Recherche Scientifique (CNRS)-IFR122-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
T-Lymphocytes
[SDV]Life Sciences [q-bio] Jurkat cells Jurkat Cells 0302 clinical medicine Cytosol NF-KappaB Inhibitor alpha ComputingMilieux_MISCELLANEOUS Ultrasonography [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology 0303 health sciences Transferrin Nuclear Proteins Coated Pits Cell-Membrane Articles Hydrogen-Ion Concentration Endocytosis 3. Good health Cell biology DNA-Binding Proteins [SDV] Life Sciences [q-bio] Protein Transport Gene Products tat [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology I-kappa B Proteins tat Gene Products Human Immunodeficiency Virus medicine.drug Interleukin 2 Transcriptional Activation Endosome Endosomes [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Twin-arginine translocation pathway 03 medical and health sciences Extracellular medicine Humans Interleukin 8 HSP90 Heat-Shock Proteins Molecular Biology [SDV.BC] Life Sciences [q-bio]/Cellular Biology 030304 developmental biology rab5 GTP-Binding Proteins Interleukin-8 Cell Biology Clathrin HIV-1 Interleukin-2 Cytokine secretion 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology of the Cell Molecular Biology of the Cell, 2004, 15 (5), pp.2347-2360. ⟨10.1091/mbc.e03-12-0921⟩ Molecular Biology of the Cell, American Society for Cell Biology, 2004, 15 (5), pp.2347-2360. ⟨10.1091/mbc.e03-12-0921⟩ |
| ISSN: | 1939-4586 |
| Popis: | The HIV-1 Tat protein is secreted by infected cells. Extracellular Tat can affect bystander uninfected T cells and induce numerous biological responses such as apoptosis and cytokine secretion. Tat is likely involved in several immune disorders during AIDS. Nevertheless, it is not known whether Tat triggers cell responses directly upon binding to signaling receptors at the plasma membrane or after delivery to the cytosol. The pathway that enables Tat to reach the cytosol is also unclear. Here we visualized Tat within T-cell–coated pits and endosomes. Moreover, inhibitors of clathrin/AP-2–mediated uptake such as chlorpromazine, activated RhoA, or dominant-negative mutants of Eps15, intersectin, dynamin, or rab5 impaired Tat delivery to the cytosol by preventing its endocytosis. Molecules neutralizing low endosomal pH or Hsp90 inhibitors abolished Tat entry at a later stage by blocking its endosomal translocation, as directly shown using a cell-free translocation assay. Finally, endosomal pH neutralization prevented Tat from inducing T-cell responses such as NF-κB activation, apoptosis, and interleukin secretion, indicating that cytosolic delivery is required for Tat signaling. Hence, Tat enters T cells essentially like diphtheria toxin, using clathrin-mediated endocytosis before low-pH–induced and Hsp90-assisted endosomal translocation. Cell responses are then induced from the cytosol. |
| Databáze: | OpenAIRE |
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