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DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation
Mast cells play a key role in the induction of anaphylaxis, a life-threatening IgE-dependent allergic reaction, by secreting chemical mediators that are stored in secretory granules. Degranulation of mast cells is triggered by aggregation of the high-affinity IgE receptor, FcεRI, and involves dynami...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076576/ https://www.ncbi.nlm.nih.gov/pubmed/24913231 http://dx.doi.org/10.1084/jem.20131926 |
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author | Ogawa, Kana Tanaka, Yoshihiko Uruno, Takehito Duan, Xuefeng Harada, Yosuke Sanematsu, Fumiyuki Yamamura, Kazuhiko Terasawa, Masao Nishikimi, Akihiko Côté, Jean-François Fukui, Yoshinori |
author_facet | Ogawa, Kana Tanaka, Yoshihiko Uruno, Takehito Duan, Xuefeng Harada, Yosuke Sanematsu, Fumiyuki Yamamura, Kazuhiko Terasawa, Masao Nishikimi, Akihiko Côté, Jean-François Fukui, Yoshinori |
author_sort | Ogawa, Kana |
collection | PubMed |
description | Mast cells play a key role in the induction of anaphylaxis, a life-threatening IgE-dependent allergic reaction, by secreting chemical mediators that are stored in secretory granules. Degranulation of mast cells is triggered by aggregation of the high-affinity IgE receptor, FcεRI, and involves dynamic rearrangement of microtubules. Although much is known about proximal signals downstream of FcεRI, the distal signaling events controlling microtubule dynamics remain elusive. Here we report that DOCK5, an atypical guanine nucleotide exchange factor (GEF) for Rac, is essential for mast cell degranulation. As such, we found that DOCK5-deficient mice exhibit resistance to systemic and cutaneous anaphylaxis. The Rac GEF activity of DOCK5 is surprisingly not required for mast cell degranulation. Instead, DOCK5 associated with Nck2 and Akt to regulate microtubule dynamics through phosphorylation and inactivation of GSK3β. When DOCK5–Nck2–Akt interactions were disrupted, microtubule formation and degranulation response were severely impaired. Our results thus identify DOCK5 as a key signaling adaptor that orchestrates remodeling of the microtubule network essential for mast cell degranulation. |
format | Online Article Text |
id | pubmed-4076576 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-40765762014-12-30 DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation Ogawa, Kana Tanaka, Yoshihiko Uruno, Takehito Duan, Xuefeng Harada, Yosuke Sanematsu, Fumiyuki Yamamura, Kazuhiko Terasawa, Masao Nishikimi, Akihiko Côté, Jean-François Fukui, Yoshinori J Exp Med Article Mast cells play a key role in the induction of anaphylaxis, a life-threatening IgE-dependent allergic reaction, by secreting chemical mediators that are stored in secretory granules. Degranulation of mast cells is triggered by aggregation of the high-affinity IgE receptor, FcεRI, and involves dynamic rearrangement of microtubules. Although much is known about proximal signals downstream of FcεRI, the distal signaling events controlling microtubule dynamics remain elusive. Here we report that DOCK5, an atypical guanine nucleotide exchange factor (GEF) for Rac, is essential for mast cell degranulation. As such, we found that DOCK5-deficient mice exhibit resistance to systemic and cutaneous anaphylaxis. The Rac GEF activity of DOCK5 is surprisingly not required for mast cell degranulation. Instead, DOCK5 associated with Nck2 and Akt to regulate microtubule dynamics through phosphorylation and inactivation of GSK3β. When DOCK5–Nck2–Akt interactions were disrupted, microtubule formation and degranulation response were severely impaired. Our results thus identify DOCK5 as a key signaling adaptor that orchestrates remodeling of the microtubule network essential for mast cell degranulation. The Rockefeller University Press 2014-06-30 /pmc/articles/PMC4076576/ /pubmed/24913231 http://dx.doi.org/10.1084/jem.20131926 Text en © 2014 Ogawa 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 Ogawa, Kana Tanaka, Yoshihiko Uruno, Takehito Duan, Xuefeng Harada, Yosuke Sanematsu, Fumiyuki Yamamura, Kazuhiko Terasawa, Masao Nishikimi, Akihiko Côté, Jean-François Fukui, Yoshinori DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation |
title | DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation |
title_full | DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation |
title_fullStr | DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation |
title_full_unstemmed | DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation |
title_short | DOCK5 functions as a key signaling adaptor that links FcεRI signals to microtubule dynamics during mast cell degranulation |
title_sort | dock5 functions as a key signaling adaptor that links fcεri signals to microtubule dynamics during mast cell degranulation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076576/ https://www.ncbi.nlm.nih.gov/pubmed/24913231 http://dx.doi.org/10.1084/jem.20131926 |
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