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TLR ligand–induced podosome disassembly in dendritic cells is ADAM17 dependent
Toll-like receptor (TLR) signaling induces a rapid reorganization of the actin cytoskeleton in cultured mouse dendritic cells (DC), leading to enhanced antigen endocytosis and a concomitant loss of filamentous actin–rich podosomes. We show that as podosomes are lost, TLR signaling induces prominent...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528573/ https://www.ncbi.nlm.nih.gov/pubmed/18762577 http://dx.doi.org/10.1083/jcb.200801022 |
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author | West, Michele A. Prescott, Alan R. Chan, Kui Ming Zhou, Zhongjun Rose-John, Stefan Scheller, Jürgen Watts, Colin |
author_facet | West, Michele A. Prescott, Alan R. Chan, Kui Ming Zhou, Zhongjun Rose-John, Stefan Scheller, Jürgen Watts, Colin |
author_sort | West, Michele A. |
collection | PubMed |
description | Toll-like receptor (TLR) signaling induces a rapid reorganization of the actin cytoskeleton in cultured mouse dendritic cells (DC), leading to enhanced antigen endocytosis and a concomitant loss of filamentous actin–rich podosomes. We show that as podosomes are lost, TLR signaling induces prominent focal contacts and a transient reduction in DC migratory capacity in vitro. We further show that podosomes in mouse DC are foci of pronounced gelatinase activity, dependent on the enzyme membrane type I matrix metalloprotease (MT1-MMP), and that DC transiently lose the ability to degrade the extracellular matrix after TLR signaling. Surprisingly, MMP inhibitors block TLR signaling–induced podosome disassembly, although stimulated endocytosis is unaffected, which demonstrates that the two phenomena are not obligatorily coupled. Podosome disassembly caused by TLR signaling occurs normally in DC lacking MT1-MMP, and instead requires the tumor necrosis factor α–converting enzyme ADAM17 (a disintegrin and metalloprotease 17), which demonstrates a novel role for this “sheddase” in regulating an actin-based structure. |
format | Text |
id | pubmed-2528573 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-25285732009-03-08 TLR ligand–induced podosome disassembly in dendritic cells is ADAM17 dependent West, Michele A. Prescott, Alan R. Chan, Kui Ming Zhou, Zhongjun Rose-John, Stefan Scheller, Jürgen Watts, Colin J Cell Biol Research Articles Toll-like receptor (TLR) signaling induces a rapid reorganization of the actin cytoskeleton in cultured mouse dendritic cells (DC), leading to enhanced antigen endocytosis and a concomitant loss of filamentous actin–rich podosomes. We show that as podosomes are lost, TLR signaling induces prominent focal contacts and a transient reduction in DC migratory capacity in vitro. We further show that podosomes in mouse DC are foci of pronounced gelatinase activity, dependent on the enzyme membrane type I matrix metalloprotease (MT1-MMP), and that DC transiently lose the ability to degrade the extracellular matrix after TLR signaling. Surprisingly, MMP inhibitors block TLR signaling–induced podosome disassembly, although stimulated endocytosis is unaffected, which demonstrates that the two phenomena are not obligatorily coupled. Podosome disassembly caused by TLR signaling occurs normally in DC lacking MT1-MMP, and instead requires the tumor necrosis factor α–converting enzyme ADAM17 (a disintegrin and metalloprotease 17), which demonstrates a novel role for this “sheddase” in regulating an actin-based structure. The Rockefeller University Press 2008-09-08 /pmc/articles/PMC2528573/ /pubmed/18762577 http://dx.doi.org/10.1083/jcb.200801022 Text en © 2008 West 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.jcb.org/misc/terms.shtml). 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 West, Michele A. Prescott, Alan R. Chan, Kui Ming Zhou, Zhongjun Rose-John, Stefan Scheller, Jürgen Watts, Colin TLR ligand–induced podosome disassembly in dendritic cells is ADAM17 dependent |
title | TLR ligand–induced podosome disassembly in dendritic cells is ADAM17 dependent |
title_full | TLR ligand–induced podosome disassembly in dendritic cells is ADAM17 dependent |
title_fullStr | TLR ligand–induced podosome disassembly in dendritic cells is ADAM17 dependent |
title_full_unstemmed | TLR ligand–induced podosome disassembly in dendritic cells is ADAM17 dependent |
title_short | TLR ligand–induced podosome disassembly in dendritic cells is ADAM17 dependent |
title_sort | tlr ligand–induced podosome disassembly in dendritic cells is adam17 dependent |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528573/ https://www.ncbi.nlm.nih.gov/pubmed/18762577 http://dx.doi.org/10.1083/jcb.200801022 |
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