ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65.
ERK regulates Golgi and centrosome orientation towards the leading edge through GRASP65.
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DOI：
10.1083/jcb.200805045
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发表时间：
2008-09-08
期刊：
影响因子：
--
通讯作者：
Seemann J
中科院分区：
文献类型：
--
作者：
Bisel B;Wang Y;Wei JH;Xiang Y;Tang D;Miron-Mendoza M;Yoshimura S;Nakamura N;Seemann J
定向细胞迁移需要高尔基体和中心体朝向前沿。我们发现，有丝分裂原表皮生长因子或溶血磷脂酸刺激间期细胞激活细胞外信号调节蛋白(ERK)，使高尔基体结构蛋白GRASP65在丝氨酸277处磷酸化。表达GRASP65 Ser277到丙氨酸突变体或GRASP65 1-201截断突变体，这两种突变体都不能被ERK磷酸化，在创伤分析中阻止高尔基体定向到前沿。我们发现，GRASP65与重组ERK的磷酸化导致GRASP65寡聚的丧失，并导致高尔基体池的去堆积。此外，通过表达突变的GRASP65来阻止高尔基体极化，可以抑制中心体定向，中心体定向在BREFELDIN A分解高尔基体结构时被拯救。我们得出结论，ERK介导的GRASP65磷酸化所介导的高尔基体重塑对于在迁移细胞中建立细胞极性至关重要。
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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