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Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient
Neutrophils respond to invading bacteria by adopting a polarized morphology, migrating in the correct direction, and engulfing the bacteria. How neutrophils establish and precisely orient this polarity toward pathogens remains unclear. Here we report that in resting neutrophils, the ERM (ezrin, radi...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322047/ https://www.ncbi.nlm.nih.gov/pubmed/25601651 http://dx.doi.org/10.1084/jem.20140508 |
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author | Liu, Xiaowen Yang, Tao Suzuki, Koya Tsukita, Sachiko Ishii, Masaru Zhou, Shuping Wang, Gang Cao, Luyang Qian, Feng Taylor, Shalina Oh, Myung-Jin Levitan, Irena Ye, Richard D. Carnegie, Graeme K. Zhao, Yong Malik, Asrar B. Xu, Jingsong |
author_facet | Liu, Xiaowen Yang, Tao Suzuki, Koya Tsukita, Sachiko Ishii, Masaru Zhou, Shuping Wang, Gang Cao, Luyang Qian, Feng Taylor, Shalina Oh, Myung-Jin Levitan, Irena Ye, Richard D. Carnegie, Graeme K. Zhao, Yong Malik, Asrar B. Xu, Jingsong |
author_sort | Liu, Xiaowen |
collection | PubMed |
description | Neutrophils respond to invading bacteria by adopting a polarized morphology, migrating in the correct direction, and engulfing the bacteria. How neutrophils establish and precisely orient this polarity toward pathogens remains unclear. Here we report that in resting neutrophils, the ERM (ezrin, radixin, and moesin) protein moesin in its active form (phosphorylated and membrane bound) prevented cell polarization by inhibiting the small GTPases Rac, Rho, and Cdc42. Attractant-induced activation of myosin phosphatase deactivated moesin at the prospective leading edge to break symmetry and establish polarity. Subsequent translocation of moesin to the trailing edge confined the formation of a prominent pseudopod directed toward pathogens and prevented secondary pseudopod formation in other directions. Therefore, both moesin-mediated inhibition and its localized deactivation by myosin phosphatase are essential for neutrophil polarization and effective neutrophil tracking of pathogens. |
format | Online Article Text |
id | pubmed-4322047 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-43220472015-08-09 Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient Liu, Xiaowen Yang, Tao Suzuki, Koya Tsukita, Sachiko Ishii, Masaru Zhou, Shuping Wang, Gang Cao, Luyang Qian, Feng Taylor, Shalina Oh, Myung-Jin Levitan, Irena Ye, Richard D. Carnegie, Graeme K. Zhao, Yong Malik, Asrar B. Xu, Jingsong J Exp Med Article Neutrophils respond to invading bacteria by adopting a polarized morphology, migrating in the correct direction, and engulfing the bacteria. How neutrophils establish and precisely orient this polarity toward pathogens remains unclear. Here we report that in resting neutrophils, the ERM (ezrin, radixin, and moesin) protein moesin in its active form (phosphorylated and membrane bound) prevented cell polarization by inhibiting the small GTPases Rac, Rho, and Cdc42. Attractant-induced activation of myosin phosphatase deactivated moesin at the prospective leading edge to break symmetry and establish polarity. Subsequent translocation of moesin to the trailing edge confined the formation of a prominent pseudopod directed toward pathogens and prevented secondary pseudopod formation in other directions. Therefore, both moesin-mediated inhibition and its localized deactivation by myosin phosphatase are essential for neutrophil polarization and effective neutrophil tracking of pathogens. The Rockefeller University Press 2015-02-09 /pmc/articles/PMC4322047/ /pubmed/25601651 http://dx.doi.org/10.1084/jem.20140508 Text en © 2015 Liu 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 | Article Liu, Xiaowen Yang, Tao Suzuki, Koya Tsukita, Sachiko Ishii, Masaru Zhou, Shuping Wang, Gang Cao, Luyang Qian, Feng Taylor, Shalina Oh, Myung-Jin Levitan, Irena Ye, Richard D. Carnegie, Graeme K. Zhao, Yong Malik, Asrar B. Xu, Jingsong Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient |
title | Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient |
title_full | Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient |
title_fullStr | Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient |
title_full_unstemmed | Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient |
title_short | Moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient |
title_sort | moesin and myosin phosphatase confine neutrophil orientation in a chemotactic gradient |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322047/ https://www.ncbi.nlm.nih.gov/pubmed/25601651 http://dx.doi.org/10.1084/jem.20140508 |
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