Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Oikawa, Tsukasa, Itoh, Toshiki, Takenawa, Tadaomi
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
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
_version_ 1782157018815004672
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
work_keys_str_mv AT oikawatsukasa sequentialsignalstowardpodosomeformationinnihsrccells
AT itohtoshiki sequentialsignalstowardpodosomeformationinnihsrccells
AT takenawatadaomi sequentialsignalstowardpodosomeformationinnihsrccells