Galectin-8 binds specific β1 integrins and induces polarized spreading highlighted by asymmetric lamellipodia in Jurkat T cells
| Autor: | Evelyn Pardo, Claudia Cárcamo, Claudia Oyanadel, Mónica Cáceres, Sergio Jacobelli, Marcela Bravo-Zehnder, Loreto Massardo, Andrea Soza, Jorge Martínez, Paulina Bull, Alfonso González |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
rac1 GTP-Binding Protein
Cytochalasin D Leukemia T-Cell Galectins Integrin Transfection Jurkat cells Thiogalactosides Jurkat Cells Cell Adhesion Humans Lupus Erythematosus Systemic Cell adhesion Cell Shape Protein Kinase Inhibitors Cytoskeleton Autoantibodies Phosphoinositide-3 Kinase Inhibitors Galectin Flavonoids Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 biology Cell adhesion molecule Integrin beta1 Antibodies Monoclonal Cell Biology Fibronectins Cell biology Androstadienes Fibronectin Galectin-8 Leukocytes Mononuclear biology.protein Cell Surface Extensions Wortmannin Protein Binding |
| Zdroj: | Experimental Cell Research. 312:374-386 |
| ISSN: | 0014-4827 |
| DOI: | 10.1016/j.yexcr.2005.10.025 |
| Popis: | Integrin-mediated encounters of T cells with extracellular cues lead these cells to adhere to a variety of substrates and acquire a spread phenotype needed for their tissue incursions. We studied the effects of galectin-8 (Gal-8), a beta-galactoside binding lectin, on Jurkat T cells. Immobilized Gal-8 bound alpha1beta1, alpha3beta1 and alpha5beta1 but not alpha2beta1 and alpha4beta1 and adhered these cells with similar kinetics to immobilized fibronectin (FN). Function-blocking experiments with monoclonal anti-integrin antibodies suggested that alpha5beta1 is the main mediator of cell adhesion to this lectin. Gal-8, but not FN, induced extensive cell spreading frequently leading to a polarized phenotype characterized by an asymmetric lamellipodial protrusion. These morphological changes involved actin cytoskeletal rearrangements controlled by PI3K, Rac-1 and ERK1/2 activity. Gal-8-induced Rac-1 activation and binding to alpha1 and alpha5 integrins have not been described in any other cellular system. Strikingly, Gal-8 was also a strong stimulus on Jurkat cells in suspension, triggering ERK1/2 activation that in most adherent cells is instead dependent on cell attachment. In addition, we found that patients with systemic lupus erythematosus (SLE), a prototypic autoimmune disorder, produce Gal-8 autoantibodies that impede both its binding to integrins and cell adhesion. These are the first function-blocking autoantibodies reported for a member of the galectin family. These results indicate that Gal-8 constitutes a novel extracellular stimulus for T cells, able to bind specific beta1 integrins and to trigger signaling pathways conducive to cell spreading. Gal-8 could modulate a wide range of T cell-driven immune processes that eventually become altered in autoimmune disorders. |
| Databáze: | OpenAIRE |
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