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Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation
Phosphatidylinositol-4,5-bisphosphate (PI4,5P(2)) is a critical regulator of cell migration, but the roles of the type I phosphatidylinositol-4-phosphate 5-kinases (PIPKIs), which synthesize PI4,5P(2), have yet to be fully defined in this process. In this study, we report that one kinase, PIPKI-α, i...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930278/ https://www.ncbi.nlm.nih.gov/pubmed/20660631 http://dx.doi.org/10.1083/jcb.200911110 |
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author | Chao, Wei-Ting Daquinag, Alexes C. Ashcroft, Felicity Kunz, Jeannette |
author_facet | Chao, Wei-Ting Daquinag, Alexes C. Ashcroft, Felicity Kunz, Jeannette |
author_sort | Chao, Wei-Ting |
collection | PubMed |
description | Phosphatidylinositol-4,5-bisphosphate (PI4,5P(2)) is a critical regulator of cell migration, but the roles of the type I phosphatidylinositol-4-phosphate 5-kinases (PIPKIs), which synthesize PI4,5P(2), have yet to be fully defined in this process. In this study, we report that one kinase, PIPKI-α, is a novel upstream regulator of Rac1 that links activated integrins to the regulation of cell migration. We show that PIPKI-α controls integrin-induced translocation of Rac1 to the plasma membrane and thereby regulates Rac1 activation. Strikingly, this function is not shared with other PIPKI isoforms, is independent of catalytic activity, and requires physical interaction of PIPKI-α with the Rac1 polybasic domain. Consistent with its role in Rac1 activation, depletion of PIPKI-α causes pronounced defects in membrane ruffling, actin organization, and focal adhesion formation, and ultimately affects the directional persistence of migration. Thus, our study defines the role of PIPKI-α in cell migration and describes a new mechanism for the spatial regulation of Rac1 activity that is critical for cell migration. |
format | Text |
id | pubmed-2930278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-29302782011-01-26 Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation Chao, Wei-Ting Daquinag, Alexes C. Ashcroft, Felicity Kunz, Jeannette J Cell Biol Research Articles Phosphatidylinositol-4,5-bisphosphate (PI4,5P(2)) is a critical regulator of cell migration, but the roles of the type I phosphatidylinositol-4-phosphate 5-kinases (PIPKIs), which synthesize PI4,5P(2), have yet to be fully defined in this process. In this study, we report that one kinase, PIPKI-α, is a novel upstream regulator of Rac1 that links activated integrins to the regulation of cell migration. We show that PIPKI-α controls integrin-induced translocation of Rac1 to the plasma membrane and thereby regulates Rac1 activation. Strikingly, this function is not shared with other PIPKI isoforms, is independent of catalytic activity, and requires physical interaction of PIPKI-α with the Rac1 polybasic domain. Consistent with its role in Rac1 activation, depletion of PIPKI-α causes pronounced defects in membrane ruffling, actin organization, and focal adhesion formation, and ultimately affects the directional persistence of migration. Thus, our study defines the role of PIPKI-α in cell migration and describes a new mechanism for the spatial regulation of Rac1 activity that is critical for cell migration. The Rockefeller University Press 2010-07-26 /pmc/articles/PMC2930278/ /pubmed/20660631 http://dx.doi.org/10.1083/jcb.200911110 Text en © 2010 Chao 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.rupress.org/terms). 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 Chao, Wei-Ting Daquinag, Alexes C. Ashcroft, Felicity Kunz, Jeannette Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation |
title | Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation |
title_full | Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation |
title_fullStr | Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation |
title_full_unstemmed | Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation |
title_short | Type I PIPK-α regulates directed cell migration by modulating Rac1 plasma membrane targeting and activation |
title_sort | type i pipk-α regulates directed cell migration by modulating rac1 plasma membrane targeting and activation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2930278/ https://www.ncbi.nlm.nih.gov/pubmed/20660631 http://dx.doi.org/10.1083/jcb.200911110 |
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