A beta2-Integrin/MRTF-A/SRF Pathway Regulates Dendritic Cell Gene Expression, Adhesion, and Traction Force Generation

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Guenther , C , Faisal , I , Uotila , L , Llort Asens , M , Harjunpää , H , Savinko , T , Öhman , T , Yao , S , Moser , M , Morris , S W , Tojkander , S & Fagerholm , S 2019 , ' A beta2-Integrin/MRTF-A/SRF Pathway Regulates Dendritic Cell Gene Expression, Adhesion, and Traction Force Generation ' , Frontiers in Immunology , vol. 10 , no. 1138 , 1138 . https://doi.org/10.3389/fimmu.2019.01138

Title: A beta2-Integrin/MRTF-A/SRF Pathway Regulates Dendritic Cell Gene Expression, Adhesion, and Traction Force Generation
Author: 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
Contributor: University of Helsinki, Integrins in immunity
University of Helsinki, External Funding
University of Helsinki, Research Services
University of Helsinki, External Funding
University of Helsinki, External Funding
University of Helsinki, Institute of Biotechnology
University of Helsinki, Soluvälitteiset voimat syöpäsolujen invaasiossa
University of Helsinki, Integrins in immunity
Date: 2019-05-28
Language: eng
Number of pages: 13
Belongs to series: Frontiers in Immunology
ISSN: 1664-3224
URI: http://hdl.handle.net/10138/304231
Abstract: 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.
Subject: 1182 Biochemistry, cell and molecular biology
DENDRITIC CELLS
ADHESION
MRTF-A/MAL-SRF pathway
LEUKOCYTE ADHESION DEFICIENCY
TRACTION FORCES
dendritic cells
adhesion
MRTF-A
SRF
MKL-1
LAD-III
traction force
SERUM RESPONSE
TRANSCRIPTION FACTOR
BETA-2 INTEGRINS
MYOCARDIN
MIGRATION
ACTIVATION
KINDLIN-3
SELECTINS
DYNAMICS
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