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DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis
Neutrophils are highly motile leukocytes, and they play important roles in the innate immune response to invading pathogens. Neutrophil chemotaxis requires Rac activation, yet the Rac activators functioning downstream of chemoattractant receptors remain to be determined. We show that DOCK2, which is...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064308/ https://www.ncbi.nlm.nih.gov/pubmed/16943182 http://dx.doi.org/10.1083/jcb.200602142 |
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author | Kunisaki, Yuya Nishikimi, Akihiko Tanaka, Yoshihiko Takii, Ryosuke Noda, Mayuko Inayoshi, Ayumi Watanabe, Ken-ichi Sanematsu, Fumiyuki Sasazuki, Takehiko Sasaki, Takehiko Fukui, Yoshinori |
author_facet | Kunisaki, Yuya Nishikimi, Akihiko Tanaka, Yoshihiko Takii, Ryosuke Noda, Mayuko Inayoshi, Ayumi Watanabe, Ken-ichi Sanematsu, Fumiyuki Sasazuki, Takehiko Sasaki, Takehiko Fukui, Yoshinori |
author_sort | Kunisaki, Yuya |
collection | PubMed |
description | Neutrophils are highly motile leukocytes, and they play important roles in the innate immune response to invading pathogens. Neutrophil chemotaxis requires Rac activation, yet the Rac activators functioning downstream of chemoattractant receptors remain to be determined. We show that DOCK2, which is a mammalian homologue of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, regulates motility and polarity during neutrophil chemotaxis. Although DOCK2-deficient neutrophils moved toward the chemoattractant source, they exhibited abnormal migratory behavior with a marked reduction in translocation speed. In DOCK2-deficient neutrophils, chemoattractant-induced activation of both Rac1 and Rac2 were severely impaired, resulting in the loss of polarized accumulation of F-actin and phosphatidylinositol 3,4,5-triphosphate (PIP(3)) at the leading edge. On the other hand, we found that DOCK2 associates with PIP(3) and translocates to the leading edge of chemotaxing neutrophils in a phosphatidylinositol 3-kinase (PI3K)–dependent manner. These results indicate that during neutrophil chemotaxis DOCK2 regulates leading edge formation through PIP(3)-dependent membrane translocation and Rac activation. |
format | Text |
id | pubmed-2064308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20643082007-11-29 DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis Kunisaki, Yuya Nishikimi, Akihiko Tanaka, Yoshihiko Takii, Ryosuke Noda, Mayuko Inayoshi, Ayumi Watanabe, Ken-ichi Sanematsu, Fumiyuki Sasazuki, Takehiko Sasaki, Takehiko Fukui, Yoshinori J Cell Biol Research Articles Neutrophils are highly motile leukocytes, and they play important roles in the innate immune response to invading pathogens. Neutrophil chemotaxis requires Rac activation, yet the Rac activators functioning downstream of chemoattractant receptors remain to be determined. We show that DOCK2, which is a mammalian homologue of Caenorhabditis elegans CED-5 and Drosophila melanogaster Myoblast City, regulates motility and polarity during neutrophil chemotaxis. Although DOCK2-deficient neutrophils moved toward the chemoattractant source, they exhibited abnormal migratory behavior with a marked reduction in translocation speed. In DOCK2-deficient neutrophils, chemoattractant-induced activation of both Rac1 and Rac2 were severely impaired, resulting in the loss of polarized accumulation of F-actin and phosphatidylinositol 3,4,5-triphosphate (PIP(3)) at the leading edge. On the other hand, we found that DOCK2 associates with PIP(3) and translocates to the leading edge of chemotaxing neutrophils in a phosphatidylinositol 3-kinase (PI3K)–dependent manner. These results indicate that during neutrophil chemotaxis DOCK2 regulates leading edge formation through PIP(3)-dependent membrane translocation and Rac activation. The Rockefeller University Press 2006-08-28 /pmc/articles/PMC2064308/ /pubmed/16943182 http://dx.doi.org/10.1083/jcb.200602142 Text en Copyright © 2006, The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Kunisaki, Yuya Nishikimi, Akihiko Tanaka, Yoshihiko Takii, Ryosuke Noda, Mayuko Inayoshi, Ayumi Watanabe, Ken-ichi Sanematsu, Fumiyuki Sasazuki, Takehiko Sasaki, Takehiko Fukui, Yoshinori DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis |
title | DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis |
title_full | DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis |
title_fullStr | DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis |
title_full_unstemmed | DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis |
title_short | DOCK2 is a Rac activator that regulates motility and polarity during neutrophil chemotaxis |
title_sort | dock2 is a rac activator that regulates motility and polarity during neutrophil chemotaxis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064308/ https://www.ncbi.nlm.nih.gov/pubmed/16943182 http://dx.doi.org/10.1083/jcb.200602142 |
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