Cargando…
Radil controls neutrophil adhesion and motility through β2-integrin activation
Integrin activation is required to facilitate multiple adhesion-dependent functions of neutrophils, such as chemotaxis, which is critical for inflammatory responses to injury and pathogens. However, little is known about the mechanisms that mediate integrin activation in neutrophils. We show that Ra...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521683/ https://www.ncbi.nlm.nih.gov/pubmed/23097489 http://dx.doi.org/10.1091/mbc.E12-05-0408 |
_version_ | 1782252979599966208 |
---|---|
author | Liu, Lunhua Aerbajinai, Wulin Ahmed, Syed M. Rodgers, Griffin P. Angers, Stephane Parent, Carole A. |
author_facet | Liu, Lunhua Aerbajinai, Wulin Ahmed, Syed M. Rodgers, Griffin P. Angers, Stephane Parent, Carole A. |
author_sort | Liu, Lunhua |
collection | PubMed |
description | Integrin activation is required to facilitate multiple adhesion-dependent functions of neutrophils, such as chemotaxis, which is critical for inflammatory responses to injury and pathogens. However, little is known about the mechanisms that mediate integrin activation in neutrophils. We show that Radil, a novel Rap1 effector, regulates β1- and β2-integrin activation and controls neutrophil chemotaxis. On activation and chemotactic migration of neutrophils, Radil quickly translocates from the cytoplasm to the plasma membrane in a Rap1a-GTP–dependent manner. Cells overexpressing Radil show a substantial increase in cell adhesion, as well as in integrin/focal adhesion kinase (FAK) activation, and exhibit an elongated morphology, with severe tail retraction defects. This phenotype is effectively rescued by treatment with either β2-integrin inhibitory antibodies or FAK inhibitors. Conversely, knockdown of Radil causes severe inhibition of cell adhesion, β2-integrin activation, and chemotaxis. Furthermore, we found that inhibition of Rap activity by RapGAP coexpression inhibits Radil-mediated integrin and FAK activation, decreases cell adhesion, and abrogates the long-tail phenotype of Radil cells. Overall, these studies establish that Radil regulates neutrophil adhesion and motility by linking Rap1 to β2-integrin activation. |
format | Online Article Text |
id | pubmed-3521683 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-35216832013-03-02 Radil controls neutrophil adhesion and motility through β2-integrin activation Liu, Lunhua Aerbajinai, Wulin Ahmed, Syed M. Rodgers, Griffin P. Angers, Stephane Parent, Carole A. Mol Biol Cell Articles Integrin activation is required to facilitate multiple adhesion-dependent functions of neutrophils, such as chemotaxis, which is critical for inflammatory responses to injury and pathogens. However, little is known about the mechanisms that mediate integrin activation in neutrophils. We show that Radil, a novel Rap1 effector, regulates β1- and β2-integrin activation and controls neutrophil chemotaxis. On activation and chemotactic migration of neutrophils, Radil quickly translocates from the cytoplasm to the plasma membrane in a Rap1a-GTP–dependent manner. Cells overexpressing Radil show a substantial increase in cell adhesion, as well as in integrin/focal adhesion kinase (FAK) activation, and exhibit an elongated morphology, with severe tail retraction defects. This phenotype is effectively rescued by treatment with either β2-integrin inhibitory antibodies or FAK inhibitors. Conversely, knockdown of Radil causes severe inhibition of cell adhesion, β2-integrin activation, and chemotaxis. Furthermore, we found that inhibition of Rap activity by RapGAP coexpression inhibits Radil-mediated integrin and FAK activation, decreases cell adhesion, and abrogates the long-tail phenotype of Radil cells. Overall, these studies establish that Radil regulates neutrophil adhesion and motility by linking Rap1 to β2-integrin activation. The American Society for Cell Biology 2012-12-15 /pmc/articles/PMC3521683/ /pubmed/23097489 http://dx.doi.org/10.1091/mbc.E12-05-0408 Text en © 2012 Liu et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Liu, Lunhua Aerbajinai, Wulin Ahmed, Syed M. Rodgers, Griffin P. Angers, Stephane Parent, Carole A. Radil controls neutrophil adhesion and motility through β2-integrin activation |
title | Radil controls neutrophil adhesion and motility through β2-integrin activation |
title_full | Radil controls neutrophil adhesion and motility through β2-integrin activation |
title_fullStr | Radil controls neutrophil adhesion and motility through β2-integrin activation |
title_full_unstemmed | Radil controls neutrophil adhesion and motility through β2-integrin activation |
title_short | Radil controls neutrophil adhesion and motility through β2-integrin activation |
title_sort | radil controls neutrophil adhesion and motility through β2-integrin activation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521683/ https://www.ncbi.nlm.nih.gov/pubmed/23097489 http://dx.doi.org/10.1091/mbc.E12-05-0408 |
work_keys_str_mv | AT liulunhua radilcontrolsneutrophiladhesionandmotilitythroughb2integrinactivation AT aerbajinaiwulin radilcontrolsneutrophiladhesionandmotilitythroughb2integrinactivation AT ahmedsyedm radilcontrolsneutrophiladhesionandmotilitythroughb2integrinactivation AT rodgersgriffinp radilcontrolsneutrophiladhesionandmotilitythroughb2integrinactivation AT angersstephane radilcontrolsneutrophiladhesionandmotilitythroughb2integrinactivation AT parentcarolea radilcontrolsneutrophiladhesionandmotilitythroughb2integrinactivation |