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Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion
Leukocytes arrested on inflamed endothelium via integrins are subjected to force imparted by flowing blood. How leukocytes respond to this force and resist detachment is poorly understood. Live-cell imaging with Lifeact-transfected U937 cells revealed that force triggers actin polymerization at upst...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317807/ https://www.ncbi.nlm.nih.gov/pubmed/22472442 http://dx.doi.org/10.1083/jcb.201107140 |
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author | Rullo, Jacob Becker, Henry Hyduk, Sharon J. Wong, Janice C. Digby, Genevieve Arora, Pamma D. Cano, Adrianet Puig Hartwig, John McCulloch, Christopher A. Cybulsky, Myron I. |
author_facet | Rullo, Jacob Becker, Henry Hyduk, Sharon J. Wong, Janice C. Digby, Genevieve Arora, Pamma D. Cano, Adrianet Puig Hartwig, John McCulloch, Christopher A. Cybulsky, Myron I. |
author_sort | Rullo, Jacob |
collection | PubMed |
description | Leukocytes arrested on inflamed endothelium via integrins are subjected to force imparted by flowing blood. How leukocytes respond to this force and resist detachment is poorly understood. Live-cell imaging with Lifeact-transfected U937 cells revealed that force triggers actin polymerization at upstream α4β1 integrin adhesion sites and the adjacent cortical cytoskeleton. Scanning electron microscopy revealed that this culminates in the formation of structures that anchor monocyte adhesion. Inhibition of actin polymerization resulted in cell deformation, displacement, and detachment. Transfection of dominant-negative constructs and inhibition of function or expression revealed key signaling steps required for upstream actin polymerization and adhesion stabilization. These included activation of Rap1, phosphoinositide 3-kinase γ isoform, and Rac but not Cdc42. Thus, rapid signaling and structural adaptations enable leukocytes to stabilize adhesion and resist detachment forces. |
format | Online Article Text |
id | pubmed-3317807 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-33178072012-10-02 Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion Rullo, Jacob Becker, Henry Hyduk, Sharon J. Wong, Janice C. Digby, Genevieve Arora, Pamma D. Cano, Adrianet Puig Hartwig, John McCulloch, Christopher A. Cybulsky, Myron I. J Cell Biol Research Articles Leukocytes arrested on inflamed endothelium via integrins are subjected to force imparted by flowing blood. How leukocytes respond to this force and resist detachment is poorly understood. Live-cell imaging with Lifeact-transfected U937 cells revealed that force triggers actin polymerization at upstream α4β1 integrin adhesion sites and the adjacent cortical cytoskeleton. Scanning electron microscopy revealed that this culminates in the formation of structures that anchor monocyte adhesion. Inhibition of actin polymerization resulted in cell deformation, displacement, and detachment. Transfection of dominant-negative constructs and inhibition of function or expression revealed key signaling steps required for upstream actin polymerization and adhesion stabilization. These included activation of Rap1, phosphoinositide 3-kinase γ isoform, and Rac but not Cdc42. Thus, rapid signaling and structural adaptations enable leukocytes to stabilize adhesion and resist detachment forces. The Rockefeller University Press 2012-04-02 /pmc/articles/PMC3317807/ /pubmed/22472442 http://dx.doi.org/10.1083/jcb.201107140 Text en © 2012 Rullo et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Rullo, Jacob Becker, Henry Hyduk, Sharon J. Wong, Janice C. Digby, Genevieve Arora, Pamma D. Cano, Adrianet Puig Hartwig, John McCulloch, Christopher A. Cybulsky, Myron I. Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion |
title | Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion |
title_full | Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion |
title_fullStr | Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion |
title_full_unstemmed | Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion |
title_short | Actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion |
title_sort | actin polymerization stabilizes α4β1 integrin anchors that mediate monocyte adhesion |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317807/ https://www.ncbi.nlm.nih.gov/pubmed/22472442 http://dx.doi.org/10.1083/jcb.201107140 |
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