Kuvaus
(TTT/AAA-b2-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-b2-integrin KI dendritic cells, which leads to a failure ofMRTF-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 b2-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 b2-integrin and kindlin-3 in integrin-mediated gene regulation and immune system function.
| Alkuperäiskieli | englanti |
|---|---|
| Artikkeli | 1138 |
| Lehti | Frontiers in Immunology |
| Vuosikerta | 10 |
| Numero | 1138 |
| Sivumäärä | 13 |
| ISSN | 1664-3224 |
| DOI - pysyväislinkit | |
| Tila | Julkaistu - 28 toukokuuta 2019 |
| OKM-julkaisutyyppi | A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu |
Tieteenalat
- 1182 Biokemia, solu- ja molekyylibiologia
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}
A beta2-Integrin/MRTF-A/SRF Pathway Regulates Dendritic Cell Gene Expression, Adhesion, and Traction Force Generation. / Guenther, Carla; Faisal, Imrul; Uotila, Liisa; Llort Asens, Marc; Harjunpää, Heidi; Savinko, Terhi; Öhman, Tiina; Yao, Sean; Moser, Markus; Morris, Stephan W.; Tojkander, Sari; Fagerholm, Susanna.
julkaisussa: Frontiers in Immunology, Vuosikerta 10, Nro 1138, 1138, 28.05.2019.Tutkimustuotos: Artikkelijulkaisu › Artikkeli › Tieteellinen › vertaisarvioitu
TY - JOUR
T1 - A beta2-Integrin/MRTF-A/SRF Pathway Regulates Dendritic Cell Gene Expression, Adhesion, and Traction Force Generation
AU - Guenther, Carla
AU - Faisal, Imrul
AU - Uotila, Liisa
AU - Llort Asens, Marc
AU - Harjunpää, Heidi
AU - Savinko, Terhi
AU - Öhman, Tiina
AU - Yao, Sean
AU - Moser, Markus
AU - Morris, Stephan W.
AU - Tojkander, Sari
AU - Fagerholm, Susanna
PY - 2019/5/28
Y1 - 2019/5/28
N2 - beta2-integrins are essential for immune system function because they mediate immune cell adhesion and signaling. Consequently, a loss of beta2-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 b2-integrin(TTT/AAA-b2-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-b2-integrin KI dendritic cells, which leads to a failure ofMRTF-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 b2-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 b2-integrin and kindlin-3 in integrin-mediated gene regulation and immune system function.
AB - beta2-integrins are essential for immune system function because they mediate immune cell adhesion and signaling. Consequently, a loss of beta2-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 b2-integrin(TTT/AAA-b2-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-b2-integrin KI dendritic cells, which leads to a failure ofMRTF-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 b2-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 b2-integrin and kindlin-3 in integrin-mediated gene regulation and immune system function.
KW - 1182 Biochemistry, cell and molecular biology
KW - DENDRITIC CELLS
KW - ADHESION
KW - MRTF-A/MAL-SRF pathway
KW - LEUKOCYTE ADHESION DEFICIENCY
KW - TRACTION FORCES
KW - dendritic cells
KW - adhesion
KW - MRTF-A
KW - SRF
KW - MKL-1
KW - LAD-III
KW - traction force
KW - SERUM RESPONSE
KW - TRANSCRIPTION FACTOR
KW - BETA-2 INTEGRINS
KW - MYOCARDIN
KW - MIGRATION
KW - ACTIVATION
KW - KINDLIN-3
KW - SELECTINS
KW - DYNAMICS
U2 - 10.3389/fimmu.2019.01138
DO - 10.3389/fimmu.2019.01138
M3 - Article
VL - 10
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - 1138
M1 - 1138
ER -