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Sequential signals toward podosome formation in NIH-src cells
Podosomes (also termed invadopodia in cancer cells) are actin-rich adhesion structures with matrix degradation activity that develop in various cell types. Despite their significant physiological importance, the molecular mechanism of podosome formation is largely unknown. In this study, we investig...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447888/ https://www.ncbi.nlm.nih.gov/pubmed/18606851 http://dx.doi.org/10.1083/jcb.200801042 |
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author | Oikawa, Tsukasa Itoh, Toshiki Takenawa, Tadaomi |
author_facet | Oikawa, Tsukasa Itoh, Toshiki Takenawa, Tadaomi |
author_sort | Oikawa, Tsukasa |
collection | PubMed |
description | Podosomes (also termed invadopodia in cancer cells) are actin-rich adhesion structures with matrix degradation activity that develop in various cell types. Despite their significant physiological importance, the molecular mechanism of podosome formation is largely unknown. In this study, we investigated the molecular mechanisms of podosome formation. The expression of various phosphoinositide-binding domains revealed that the podosomes in Src-transformed NIH3T3 (NIH-src) cells are enriched with PtdIns(3,4)P2, suggesting an important role of this phosphoinositide in podosome formation. Live-cell imaging analysis revealed that Src-expression stimulated podosome formation at focal adhesions of NIH3T3 cells after PtdIns(3,4)P2 accumulation. The adaptor protein Tks5/FISH, which is essential for podosome formation, was found to form a complex with Grb2 at adhesion sites in an Src-dependent manner. Further, it was found that N-WASP bound all SH3 domains of Tks5/FISH, which facilitated circular podosome formation. These results indicate that augmentation of the N-WASP–Arp2/3 signal was accomplished on the platform of Tks5/FISH-Grb2 complex at focal adhesions, which is stabilized by PtdIns(3,4)P2. |
format | Text |
id | pubmed-2447888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-24478882009-01-14 Sequential signals toward podosome formation in NIH-src cells Oikawa, Tsukasa Itoh, Toshiki Takenawa, Tadaomi J Cell Biol Research Articles Podosomes (also termed invadopodia in cancer cells) are actin-rich adhesion structures with matrix degradation activity that develop in various cell types. Despite their significant physiological importance, the molecular mechanism of podosome formation is largely unknown. In this study, we investigated the molecular mechanisms of podosome formation. The expression of various phosphoinositide-binding domains revealed that the podosomes in Src-transformed NIH3T3 (NIH-src) cells are enriched with PtdIns(3,4)P2, suggesting an important role of this phosphoinositide in podosome formation. Live-cell imaging analysis revealed that Src-expression stimulated podosome formation at focal adhesions of NIH3T3 cells after PtdIns(3,4)P2 accumulation. The adaptor protein Tks5/FISH, which is essential for podosome formation, was found to form a complex with Grb2 at adhesion sites in an Src-dependent manner. Further, it was found that N-WASP bound all SH3 domains of Tks5/FISH, which facilitated circular podosome formation. These results indicate that augmentation of the N-WASP–Arp2/3 signal was accomplished on the platform of Tks5/FISH-Grb2 complex at focal adhesions, which is stabilized by PtdIns(3,4)P2. The Rockefeller University Press 2008-07-14 /pmc/articles/PMC2447888/ /pubmed/18606851 http://dx.doi.org/10.1083/jcb.200801042 Text en © 2008 Oikawa 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 Oikawa, Tsukasa Itoh, Toshiki Takenawa, Tadaomi Sequential signals toward podosome formation in NIH-src cells |
title | Sequential signals toward podosome formation in NIH-src cells |
title_full | Sequential signals toward podosome formation in NIH-src cells |
title_fullStr | Sequential signals toward podosome formation in NIH-src cells |
title_full_unstemmed | Sequential signals toward podosome formation in NIH-src cells |
title_short | Sequential signals toward podosome formation in NIH-src cells |
title_sort | sequential signals toward podosome formation in nih-src cells |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447888/ https://www.ncbi.nlm.nih.gov/pubmed/18606851 http://dx.doi.org/10.1083/jcb.200801042 |
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