IRSp53 Mediates Podosome Formation via VASP in NIH-Src Cells

IRSp53 Mediates Podosome Formation via VASP in NIH-Src Cells

Podosomes are cellular “feet,” characterized by F-actin-rich membrane protrusions, which drive cell migration and invasion into the extracellular matrix. Small GTPases that regulate the actin cytoskeleton, such as Cdc42 and Rac are central regulators of podosome formation. The adaptor protein IRSp53...

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Main Authors: Oikawa, Tsukasa, Okamura, Hitomi, Dietrich, Franziska, Senju, Yosuke, Takenawa, Tadaomi, Suetsugu, Shiro
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608619/
id pubmed-3608619
recordtype oai_dc
spelling pubmed-36086192013-04-03 IRSp53 Mediates Podosome Formation via VASP in NIH-Src Cells Oikawa, Tsukasa Okamura, Hitomi Dietrich, Franziska Senju, Yosuke Takenawa, Tadaomi Suetsugu, Shiro Research Article Podosomes are cellular “feet,” characterized by F-actin-rich membrane protrusions, which drive cell migration and invasion into the extracellular matrix. Small GTPases that regulate the actin cytoskeleton, such as Cdc42 and Rac are central regulators of podosome formation. The adaptor protein IRSp53 contains an I-BAR domain that deforms membranes into protrusions and binds to Rac, a CRIB motif that interacts with Cdc42, an SH3 domain that binds to many actin cytoskeletal regulators with proline-rich peptides including VASP, and the C-terminal variable region by splicing. However, the role of IRSp53 and VASP in podosome formation had been unclear. Here we found that the knockdown of IRSp53 by RNAi attenuates podosome formation and migration in Src-transformed NIH3T3 (NIH-Src) cells. Importantly, the differences in the IRSp53 C-terminal splicing isoforms did not affect podosome formation. Overexpression of IRSp53 deletion mutants suggested the importance of linking small GTPases to SH3 binding partners. Interestingly, VASP physically interacted with IRSp53 in NIH-Src cells and was essential for podosome formation. These data highlight the role of IRSp53 as a linker of small GTPases to VASP for podosome formation. Public Library of Science 2013-03-26 /pmc/articles/PMC3608619/ /pubmed/23555988 http://dx.doi.org/10.1371/journal.pone.0060528 Text en © 2013 Oikawa et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Oikawa, Tsukasa
Okamura, Hitomi
Dietrich, Franziska
Senju, Yosuke
Takenawa, Tadaomi
Suetsugu, Shiro
spellingShingle Oikawa, Tsukasa
Okamura, Hitomi
Dietrich, Franziska
Senju, Yosuke
Takenawa, Tadaomi
Suetsugu, Shiro
IRSp53 Mediates Podosome Formation via VASP in NIH-Src Cells
author_facet Oikawa, Tsukasa
Okamura, Hitomi
Dietrich, Franziska
Senju, Yosuke
Takenawa, Tadaomi
Suetsugu, Shiro
author_sort Oikawa, Tsukasa
title IRSp53 Mediates Podosome Formation via VASP in NIH-Src Cells
title_short IRSp53 Mediates Podosome Formation via VASP in NIH-Src Cells
title_full IRSp53 Mediates Podosome Formation via VASP in NIH-Src Cells
title_fullStr IRSp53 Mediates Podosome Formation via VASP in NIH-Src Cells
title_full_unstemmed IRSp53 Mediates Podosome Formation via VASP in NIH-Src Cells
title_sort irsp53 mediates podosome formation via vasp in nih-src cells
description Podosomes are cellular “feet,” characterized by F-actin-rich membrane protrusions, which drive cell migration and invasion into the extracellular matrix. Small GTPases that regulate the actin cytoskeleton, such as Cdc42 and Rac are central regulators of podosome formation. The adaptor protein IRSp53 contains an I-BAR domain that deforms membranes into protrusions and binds to Rac, a CRIB motif that interacts with Cdc42, an SH3 domain that binds to many actin cytoskeletal regulators with proline-rich peptides including VASP, and the C-terminal variable region by splicing. However, the role of IRSp53 and VASP in podosome formation had been unclear. Here we found that the knockdown of IRSp53 by RNAi attenuates podosome formation and migration in Src-transformed NIH3T3 (NIH-Src) cells. Importantly, the differences in the IRSp53 C-terminal splicing isoforms did not affect podosome formation. Overexpression of IRSp53 deletion mutants suggested the importance of linking small GTPases to SH3 binding partners. Interestingly, VASP physically interacted with IRSp53 in NIH-Src cells and was essential for podosome formation. These data highlight the role of IRSp53 as a linker of small GTPases to VASP for podosome formation.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608619/
_version_ 1611965494700539904

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