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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2014
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.
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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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