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ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65

Directed cell migration requires the orientation of the Golgi and centrosome toward the leading edge. We show that stimulation of interphase cells with the mitogens epidermal growth factor or lysophosphatidic acid activates the extracellular signal–regulated kinase (ERK), which phosphorylates the Go...

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Autores principales: Bisel, Blaine, Wang, Yanzhuang, Wei, Jen-Hsuan, Xiang, Yi, Tang, Danming, Miron-Mendoza, Miguel, Yoshimura, Shin-ichiro, Nakamura, Nobuhiro, Seemann, Joachim
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528584/
https://www.ncbi.nlm.nih.gov/pubmed/18762583
http://dx.doi.org/10.1083/jcb.200805045
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author Bisel, Blaine
Wang, Yanzhuang
Wei, Jen-Hsuan
Xiang, Yi
Tang, Danming
Miron-Mendoza, Miguel
Yoshimura, Shin-ichiro
Nakamura, Nobuhiro
Seemann, Joachim
author_facet Bisel, Blaine
Wang, Yanzhuang
Wei, Jen-Hsuan
Xiang, Yi
Tang, Danming
Miron-Mendoza, Miguel
Yoshimura, Shin-ichiro
Nakamura, Nobuhiro
Seemann, Joachim
author_sort Bisel, Blaine
collection PubMed
description Directed cell migration requires the orientation of the Golgi and centrosome toward the leading edge. We show that stimulation of interphase cells with the mitogens epidermal growth factor or lysophosphatidic acid activates the extracellular signal–regulated kinase (ERK), which phosphorylates the Golgi structural protein GRASP65 at serine 277. Expression of a GRASP65 Ser277 to alanine mutant or a GRASP65 1–201 truncation mutant, neither of which can be phosphorylated by ERK, prevents Golgi orientation to the leading edge in a wound assay. We show that phosphorylation of GRASP65 with recombinant ERK leads to the loss of GRASP65 oligomerization and causes Golgi cisternal unstacking. Furthermore, preventing Golgi polarization by expressing mutated GRASP65 inhibits centrosome orientation, which is rescued upon disassembly of the Golgi structure by brefeldin A. We conclude that Golgi remodeling, mediated by phosphorylation of GRASP65 by ERK, is critical for the establishment of cell polarity in migrating cells.
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spelling pubmed-25285842009-03-08 ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65 Bisel, Blaine Wang, Yanzhuang Wei, Jen-Hsuan Xiang, Yi Tang, Danming Miron-Mendoza, Miguel Yoshimura, Shin-ichiro Nakamura, Nobuhiro Seemann, Joachim J Cell Biol Research Articles Directed cell migration requires the orientation of the Golgi and centrosome toward the leading edge. We show that stimulation of interphase cells with the mitogens epidermal growth factor or lysophosphatidic acid activates the extracellular signal–regulated kinase (ERK), which phosphorylates the Golgi structural protein GRASP65 at serine 277. Expression of a GRASP65 Ser277 to alanine mutant or a GRASP65 1–201 truncation mutant, neither of which can be phosphorylated by ERK, prevents Golgi orientation to the leading edge in a wound assay. We show that phosphorylation of GRASP65 with recombinant ERK leads to the loss of GRASP65 oligomerization and causes Golgi cisternal unstacking. Furthermore, preventing Golgi polarization by expressing mutated GRASP65 inhibits centrosome orientation, which is rescued upon disassembly of the Golgi structure by brefeldin A. We conclude that Golgi remodeling, mediated by phosphorylation of GRASP65 by ERK, is critical for the establishment of cell polarity in migrating cells. The Rockefeller University Press 2008-09-08 /pmc/articles/PMC2528584/ /pubmed/18762583 http://dx.doi.org/10.1083/jcb.200805045 Text en © 2008 Bisel 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.jcb.org/misc/terms.shtml). 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
Bisel, Blaine
Wang, Yanzhuang
Wei, Jen-Hsuan
Xiang, Yi
Tang, Danming
Miron-Mendoza, Miguel
Yoshimura, Shin-ichiro
Nakamura, Nobuhiro
Seemann, Joachim
ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65
title ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65
title_full ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65
title_fullStr ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65
title_full_unstemmed ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65
title_short ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65
title_sort erk regulates golgi and centrosome orientation towards the leading edge through grasp65
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528584/
https://www.ncbi.nlm.nih.gov/pubmed/18762583
http://dx.doi.org/10.1083/jcb.200805045
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