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Integrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells()
Podosomes are integrin-based adhesions fundamental for stabilisation of the leading lamellae in migrating dendritic cells (DCs) and for extracellular matrix (ECM) degradation. We have previously shown that soluble factors and chemokines such as SDF 1-a trigger podosome initiation whereas integrin li...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998073/ https://www.ncbi.nlm.nih.gov/pubmed/24508783 http://dx.doi.org/10.1016/j.biocel.2014.01.021 |
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author | Griera, Mercedes Martin-Villar, Ester Banon-Rodríguez, Inmaculada Blundell, Michael P. Jones, Gareth E. Anton, Ines M. Thrasher, Adrian J. Rodriguez-Puyol, Manuel Calle, Yolanda |
author_facet | Griera, Mercedes Martin-Villar, Ester Banon-Rodríguez, Inmaculada Blundell, Michael P. Jones, Gareth E. Anton, Ines M. Thrasher, Adrian J. Rodriguez-Puyol, Manuel Calle, Yolanda |
author_sort | Griera, Mercedes |
collection | PubMed |
description | Podosomes are integrin-based adhesions fundamental for stabilisation of the leading lamellae in migrating dendritic cells (DCs) and for extracellular matrix (ECM) degradation. We have previously shown that soluble factors and chemokines such as SDF 1-a trigger podosome initiation whereas integrin ligands promote podosome maturation and stability in DCs. The exact intracellular signalling pathways that regulate the sequential organisation of podosomal components in response to extracellular cues remain largely undetermined. The Wiskott Aldrich Syndrome Protein (WASP) mediates actin polymerisation and the initial recruitment of integrins and associated proteins in a circular configuration surrounding the core of filamentous actin (F-actin) during podosome initiation. We have now identified integrin linked kinase (ILK) surrounding the podosomal actin core. We report that DC polarisation in response to chemokines and the assembly of actin cores during podosome initiation require PI3K-dependent clustering of the Wiskott Aldrich Syndrome Protein (WASP) in puncta independently of ILK. ILK is essential for the clustering of integrins and associated proteins leading to podosome maturation and stability that are required for degradation of the subjacent extracellular matrix and the invasive motility of DCs across connective tissue barriers. We conclude that WASP regulates DCs polarisation for migration and initiation of actin polymerisation downstream of PI3K in nascent podosomes. Subsequently, ILK mediates the accumulation of integrin-associated proteins during podosome maturation and stability for efficient degradation of the subjacent ECM during the invasive migration of DCs. |
format | Online Article Text |
id | pubmed-3998073 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-39980732014-05-01 Integrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells() Griera, Mercedes Martin-Villar, Ester Banon-Rodríguez, Inmaculada Blundell, Michael P. Jones, Gareth E. Anton, Ines M. Thrasher, Adrian J. Rodriguez-Puyol, Manuel Calle, Yolanda Int J Biochem Cell Biol Article Podosomes are integrin-based adhesions fundamental for stabilisation of the leading lamellae in migrating dendritic cells (DCs) and for extracellular matrix (ECM) degradation. We have previously shown that soluble factors and chemokines such as SDF 1-a trigger podosome initiation whereas integrin ligands promote podosome maturation and stability in DCs. The exact intracellular signalling pathways that regulate the sequential organisation of podosomal components in response to extracellular cues remain largely undetermined. The Wiskott Aldrich Syndrome Protein (WASP) mediates actin polymerisation and the initial recruitment of integrins and associated proteins in a circular configuration surrounding the core of filamentous actin (F-actin) during podosome initiation. We have now identified integrin linked kinase (ILK) surrounding the podosomal actin core. We report that DC polarisation in response to chemokines and the assembly of actin cores during podosome initiation require PI3K-dependent clustering of the Wiskott Aldrich Syndrome Protein (WASP) in puncta independently of ILK. ILK is essential for the clustering of integrins and associated proteins leading to podosome maturation and stability that are required for degradation of the subjacent extracellular matrix and the invasive motility of DCs across connective tissue barriers. We conclude that WASP regulates DCs polarisation for migration and initiation of actin polymerisation downstream of PI3K in nascent podosomes. Subsequently, ILK mediates the accumulation of integrin-associated proteins during podosome maturation and stability for efficient degradation of the subjacent ECM during the invasive migration of DCs. Elsevier 2014-05 /pmc/articles/PMC3998073/ /pubmed/24508783 http://dx.doi.org/10.1016/j.biocel.2014.01.021 Text en Crown Copyright © 2014 Published by Elsevier Ltd. http://creativecommons.org/licenses/by/3.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Griera, Mercedes Martin-Villar, Ester Banon-Rodríguez, Inmaculada Blundell, Michael P. Jones, Gareth E. Anton, Ines M. Thrasher, Adrian J. Rodriguez-Puyol, Manuel Calle, Yolanda Integrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells() |
title | Integrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells() |
title_full | Integrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells() |
title_fullStr | Integrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells() |
title_full_unstemmed | Integrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells() |
title_short | Integrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells() |
title_sort | integrin linked kinase (ilk) regulates podosome maturation and stability in dendritic cells() |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998073/ https://www.ncbi.nlm.nih.gov/pubmed/24508783 http://dx.doi.org/10.1016/j.biocel.2014.01.021 |
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