Helicobacter pylori VacA cytotoxin: a probe for a clathrin-independent and Cdc42-dependent pinocytic pathway routed to late endosomes
| Autor: | V. Kaddai, Nils C. Gauthier, Pascale Monzo, Anne Doye, Patrice Boquet, Vittorio Ricci |
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| Přispěvatelé: | Toxines bactériennes dans la relation hôtes-pathogènes, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Signalisation moléculaire et obésité, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Human Physiology Section, Department of Experimental Medicine, Università degli Studi di Pavia, Lemichez, Emmanuel, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Università degli Studi di Pavia = University of Pavia (UNIPV) |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
rac1 GTP-Binding Protein
MESH: ADP-Ribosylation Factors Endocytic cycle Caveolin 1 Vesicular Transport Proteins MESH: Membrane Microdomains Dynamin II MESH: Caveolin 1 MESH: Clathrin cdc42 GTP-Binding Protein Lipid raft MESH: Bacterial Proteins 0303 health sciences biology ADP-Ribosylation Factors Pinocytosis 030302 biochemistry & molecular biology Transferrin Articles Cell biology [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Cdc42 GTP-Binding Protein MESH: Cell Adhesion Molecules MESH: Membrane Proteins Endosome Virulence Factors Bacterial Toxins Endosomes [SDV.BC]Life Sciences [q-bio]/Cellular Biology MESH: Actins Clathrin Cell Line EEA1 03 medical and health sciences Membrane Microdomains Bacterial Proteins Humans [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology [SDV.BC] Life Sciences [q-bio]/Cellular Biology Molecular Biology 030304 developmental biology Dynamin rab5 GTP-Binding Proteins MESH: Humans Helicobacter pylori MESH: Research Support Membrane Proteins Cell Biology bacterial infections and mycoses MESH: Pinocytosis Actins digestive system diseases MESH: Cell Line MESH: Bacterial Toxins ADP-Ribosylation Factor 6 MESH: Endosomes MESH: Dynamin II biology.protein bacteria MESH: Helicobacter pylori rhoA GTP-Binding Protein Cell Adhesion Molecules |
| Zdroj: | Molecular Biology of the Cell Molecular Biology of the Cell, American Society for Cell Biology, 2005, 16, pp.4852-66. ⟨10.1091/mbc.E05-05-0398⟩ Molecular Biology of the Cell, 2005, 16, pp.4852-66. ⟨10.1091/mbc.E05-05-0398⟩ |
| ISSN: | 1939-4586 |
| DOI: | 10.1091/mbc.E05-05-0398⟩ |
| Popis: | The vacuolating cytotoxin VacA is a major virulence factor of Helicobacter pylori, a bacterium responsible for gastroduodenal ulcers and cancer. VacA associates with lipid rafts, is endocytosed, and reaches the late endocytic compartment where it induces vacuolation. We have investigated the endocytic and intracellular trafficking pathways used by VacA, in HeLa and gastric AGS cells. We report here that VacA was first bound to plasma-membrane domains localized above F-actin structures that were controlled by the Rac1 GTPase. VacA was subsequently pinocytosed by a clathrin-independent mechanism into cell peripheral early endocytic compartments lacking caveolin 1, the Rab5 effector early endosomes antigen-1 (EEA1) and transferrin. These compartments took up fluid-phase (as evidenced by the accumulation of fluorescent dextran) and glycosylphosphatidylinositol-anchored proteins (GPI-APs). VacA pinocytosis was controlled by Cdc42 and did not require cellular tyrosine kinases, dynamin 2, ADP-ribosylating factor 6, or RhoA GTPase activities. VacA was subsequently routed to EEA1-sorting endosomes and then sorted to late endosomes. During all these different endocytic steps, VacA was continuously associated with detergent resistant membrane domains. From these results we propose that VacA might be a valuable probe to study raft-associated molecules, pinocytosed by a clathrin-independent mechanism, and routed to the degradative compartment. |
| Databáze: | OpenAIRE |
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