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The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes
Podosomes are actin-based matrix contacts in a variety of cell types, most notably monocytic cells, and are characterized by their ability to lyse extracellular matrix material. Besides their dependence on actin regulation, podosomes are also influenced by microtubules and microtubule-dependent tran...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020916/ https://www.ncbi.nlm.nih.gov/pubmed/21119006 http://dx.doi.org/10.1091/mbc.E10-05-0394 |
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author | Cornfine, Susanne Himmel, Mirko Kopp, Petra el Azzouzi, Karim Wiesner, Christiane Krüger, Marcus Rudel, Thomas Linder, Stefan |
author_facet | Cornfine, Susanne Himmel, Mirko Kopp, Petra el Azzouzi, Karim Wiesner, Christiane Krüger, Marcus Rudel, Thomas Linder, Stefan |
author_sort | Cornfine, Susanne |
collection | PubMed |
description | Podosomes are actin-based matrix contacts in a variety of cell types, most notably monocytic cells, and are characterized by their ability to lyse extracellular matrix material. Besides their dependence on actin regulation, podosomes are also influenced by microtubules and microtubule-dependent transport processes. Here we describe a novel role for KIF9, a previously little-characterized member of the kinesin motor family, in the regulation of podosomes in primary human macrophages. We find that small interfering RNA (siRNA)/short-hairpin RNA–induced knockdown of KIF9 significantly affects both numbers and matrix degradation of podosomes. Overexpression and microinjection experiments reveal that the unique C-terminal region of KIF9 is crucial for these effects, presumably through binding of specific interactors. Indeed, we further identify reggie-1/flotillin-2, a signaling mediator between intracellular vesicles and the cell periphery, as an interactor of the KIF9 C-terminus. Reggie-1 dynamically colocalizes with KIF9 in living cells, and, consistent with KIF9-mediated effects, siRNA-induced knockdown of reggies/flotillins significantly impairs matrix degradation by podosomes. In sum, we identify the kinesin KIF9 and reggie/flotillin proteins as novel regulators of macrophage podosomes and show that their interaction is critical for the matrix-degrading ability of these structures. |
format | Text |
id | pubmed-3020916 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-30209162011-03-30 The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes Cornfine, Susanne Himmel, Mirko Kopp, Petra el Azzouzi, Karim Wiesner, Christiane Krüger, Marcus Rudel, Thomas Linder, Stefan Mol Biol Cell Articles Podosomes are actin-based matrix contacts in a variety of cell types, most notably monocytic cells, and are characterized by their ability to lyse extracellular matrix material. Besides their dependence on actin regulation, podosomes are also influenced by microtubules and microtubule-dependent transport processes. Here we describe a novel role for KIF9, a previously little-characterized member of the kinesin motor family, in the regulation of podosomes in primary human macrophages. We find that small interfering RNA (siRNA)/short-hairpin RNA–induced knockdown of KIF9 significantly affects both numbers and matrix degradation of podosomes. Overexpression and microinjection experiments reveal that the unique C-terminal region of KIF9 is crucial for these effects, presumably through binding of specific interactors. Indeed, we further identify reggie-1/flotillin-2, a signaling mediator between intracellular vesicles and the cell periphery, as an interactor of the KIF9 C-terminus. Reggie-1 dynamically colocalizes with KIF9 in living cells, and, consistent with KIF9-mediated effects, siRNA-induced knockdown of reggies/flotillins significantly impairs matrix degradation by podosomes. In sum, we identify the kinesin KIF9 and reggie/flotillin proteins as novel regulators of macrophage podosomes and show that their interaction is critical for the matrix-degrading ability of these structures. The American Society for Cell Biology 2011-01-15 /pmc/articles/PMC3020916/ /pubmed/21119006 http://dx.doi.org/10.1091/mbc.E10-05-0394 Text en © 2011 Cornfine 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 Biology. |
spellingShingle | Articles Cornfine, Susanne Himmel, Mirko Kopp, Petra el Azzouzi, Karim Wiesner, Christiane Krüger, Marcus Rudel, Thomas Linder, Stefan The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes |
title | The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes |
title_full | The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes |
title_fullStr | The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes |
title_full_unstemmed | The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes |
title_short | The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes |
title_sort | kinesin kif9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020916/ https://www.ncbi.nlm.nih.gov/pubmed/21119006 http://dx.doi.org/10.1091/mbc.E10-05-0394 |
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