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

Blaine Bisel, Yanzhuang Wang, Jen Hsuan Wei, Yi Xiang, Danming Tang, Miguel Miron-Mendoza, Shin Ichiro Yoshimura, Nobuhiro Nakamura, Joachim Seemann

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

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 phosphoryl ation of GRASP65 by ERK, is critical for the establishment of cell polarity in migrating cells.

Original languageEnglish (US)
Pages (from-to)837-843
Number of pages7
JournalJournal of Cell Biology
Volume182
Issue number5
DOIs
StatePublished - Sep 8 2008

ASJC Scopus subject areas

  • Cell Biology

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    Bisel, B., Wang, Y., Wei, J. H., Xiang, Y., Tang, D., Miron-Mendoza, M., Yoshimura, S. I., Nakamura, N., & Seemann, J. (2008). ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65. Journal of Cell Biology, 182(5), 837-843. https://doi.org/10.1083/jcb.200805045