English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  A beta 2-Integrin/MRTF-A/SRF Pathway Regulates Dendritic Cell Gene Expression, Adhesion, and Traction Force Generation

Guenther, C., Faisal, I., Uotila, L. M., Asens, M. L., Harjunpaa, H., Savinko, T., et al. (2019). A beta 2-Integrin/MRTF-A/SRF Pathway Regulates Dendritic Cell Gene Expression, Adhesion, and Traction Force Generation. Frontiers in immunology, 10: 1138. doi:10.3389/fimmu.2019.01138.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files
hide Files
:
fimmu-10-01138.pdf (Publisher version), 8MB
Name:
fimmu-10-01138.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
© 2019 Guenther, Faisal, Uotila, Asens, Harjunpää, Savinko, Öhman, Yao, Moser, Morris, Tojkander and Fagerholm.
:
4519277.zip (Supplementary material), 1006KB
Name:
4519277.zip
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/zip / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Guenther, Carla1, Author
Faisal, Imrul1, Author
Uotila, Liisa M.1, Author
Asens, Marc Llort1, Author
Harjunpaa, Heidi1, Author
Savinko, Terhi1, Author
Ohman, Tiina1, Author
Yao, Sean1, Author
Moser, Markus2, Author              
Morris, Stephan W.1, Author
Tojkander, Sari1, Author
Fagerholm, Susanna Carola1, Author
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

Content

show
hide
Free keywords: SERUM RESPONSE; TRANSCRIPTION FACTOR; BETA-2 INTEGRINS; MYOCARDIN; MIGRATION; SRF; ACTIVATION; KINDLIN-3; SELECTINS; DYNAMICSImmunology; dendritic cells; adhesion; MRTF-A; SRF; MKL-1; LAD-III; traction force;
 Abstract: 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.

Details

show
hide
Language(s): eng - English
 Dates: 2019
 Publication Status: Published online
 Pages: 13
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000469267900001
DOI: 10.3389/fimmu.2019.01138
 Degree: -

Event

show

Legal Case

show

Project information

show hide
Project name : SFB914, project A1
Grant ID : -
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft

Source 1

show
hide
Title: Frontiers in immunology
  Abbreviation : Front immunol
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Lausanne : Frontiers Media
Pages: - Volume / Issue: 10 Sequence Number: 1138 Start / End Page: - Identifier: ISSN: 1664-3224
CoNE: https://pure.mpg.de/cone/journals/resource/1664-3224