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Integrin linked kinase (ILK) regulates podosome maturation and stability in dendritic cells.
- Source :
-
The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2014 May; Vol. 50, pp. 47-54. Date of Electronic Publication: 2014 Feb 06. - Publication Year :
- 2014
-
Abstract
- 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.<br /> (Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Cell Membrane Structures enzymology
Cell Movement physiology
Dendritic Cells metabolism
Extracellular Matrix metabolism
Humans
Male
Mice
Mice, Inbred C57BL
Phosphatidylinositol 3-Kinases metabolism
Transfection
Wiskott-Aldrich Syndrome Protein metabolism
Dendritic Cells cytology
Dendritic Cells enzymology
Protein Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5875
- Volume :
- 50
- Database :
- MEDLINE
- Journal :
- The international journal of biochemistry & cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 24508783
- Full Text :
- https://doi.org/10.1016/j.biocel.2014.01.021