A beta 2-Integrin/MRTF-A/SRF Pathway Regulates Dendritic Cell Gene Expression, Adhesion, and Traction Force Generation
| Autor: | Carla Guenther, Imrul Faisal, Liisa M. Uotila, Marc Llort Asens, Heidi Harjunpää, Terhi Savinko, Tiina Öhman, Sean Yao, Markus Moser, Stephan W. Morris, Sari Tojkander, Susanna Carola Fagerholm |
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| Přispěvatelé: | Integrins in immunity, External Funding, Research Services, Institute of Biotechnology, Soluvälitteiset voimat syöpäsolujen invaasiossa, Veterinary Biosciences, Helsinki One Health (HOH), Molecular Systems Biology |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
DYNAMICS Serum Response Factor BETA-2 INTEGRINS RHOA MYOCARDIN LEUKOCYTE ADHESION DEFICIENCY ADHESION ACTIVATION 0302 clinical medicine Cell Movement Immunology and Allergy Gene Regulatory Networks TRANSCRIPTION FACTOR Cells Cultured Original Research Regulation of gene expression Mice Knockout biology Chemistry SELECTINS Cell biology Biomechanical Phenomena SERUM RESPONSE cardiovascular system SRF Signal transduction Signal Transduction lcsh:Immunologic diseases. Allergy MIGRATION Integrin Immunology TRACTION FORCES LAD-III traction force Mice Transgenic DENDRITIC CELLS 03 medical and health sciences Serum response factor MRTF-A/MAL-SRF pathway medicine Cell Adhesion Animals Cell adhesion Leukocyte adhesion deficiency Gene Expression Profiling MKL-1 Dendritic cell medicine.disease KINDLIN-3 Mice Inbred C57BL Cytoskeletal Proteins 030104 developmental biology Gene Ontology MRTF-A CD18 Antigens biology.protein Trans-Activators 1182 Biochemistry cell and molecular biology rhoA GTP-Binding Protein lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in immunology Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology |
| Popis: | beta 2-integrins are essential for immune system function because they mediate immune cell adhesion and signaling. Consequently, a loss of beta(2)-integrin expression or function causes the immunodeficiency disorders, Leukocyte Adhesion Deficiency (LAD) type I and III. LAD-III is caused by mutations in an important integrin regulator, kindlin-3, but exactly how kindlin-3 regulates leukocyte adhesion has remained incompletely understood. Here we demonstrate that mutation of the kindlin-3 binding site in the beta 2-integrin (TTT/AAA-beta 2-integrin knock-in mouse/KI) abolishes activation of the actin-regulated myocardin related transcription factor A/serum response factor (MRTF-A/SRF) signaling pathway in dendritic cells and MRTF-A/SRF-dependent gene expression. We show that Ras homolog gene family, member A (RhoA) activation and filamentous-actin (F-actin) polymerization is abolished in murine TTT/AAA-beta 2-integrin KI dendritic cells, which leads to a failure of MRTF-A to localize to the cell nucleus to coactivate genes together with SRF. In addition, we show that dendritic cell gene expression, adhesion and integrin-mediated traction forces on ligand coated surfaces is dependent on the MRTF-A/SRF signaling pathway. The participation of beta 2-integrin and kindlin-3-mediated cell adhesion in the regulation of the ubiquitous MRTF-A/SRF signaling pathway in immune cells may help explain the role of beta 2-integrin and kindlin-3 in integrin-mediated gene regulation and immune system function. |
| Databáze: | OpenAIRE |
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