The novel RacE-binding protein GflB sharpens Ras activity at the leading edge of migrating cells
The novel RacE-binding protein GflB sharpens Ras activity at the leading edge of migrating cells
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DOI：
10.1091/mbc.e15-11-0796
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发表时间：
2016-05-15
影响因子：
3.3
通讯作者：
Iijima, Miho
中科院分区：
文献类型：
--
作者：
Senoo, Hiroshi;Cai, Huaqing;Iijima, Miho
定向传感是细胞将外部化学梯度转化为内部信号事件的过程，对于趋化性至关重要。我们之前表明 Rho GTP 酶 RacE 调节盘基网柄菌细胞中的梯度感应。在这里，利用亲和纯化和质谱分析，我们鉴定了一种新型 RacE 结合蛋白 GflB，它包含 Ras GEF 结构域和 Rho GAP 结构域。使用生化和基因敲除方法，我们发现 GflB 平衡 Ras 和 Rho GTPases 的激活，使细胞能够精确地将信号事件导向更高浓度的化学引诱剂。此外，我们发现GflB位于迁移细胞的前缘，并且这种定位受到肌动蛋白细胞骨架和磷脂酰丝氨酸的调节。我们的研究结果提供了一种连接方向传感和形态偏振的新分子机制。
Directional sensing, a process in which cells convert an external chemical gradient into internal signaling events, is essential in chemotaxis. We previously showed that a Rho GTPase, RacE, regulates gradient sensing in Dictyostelium cells. Here, using affinity purification and mass spectrometry, we identify a novel RacE-binding protein, GflB, which contains a Ras GEF domain and a Rho GAP domain. Using biochemical and gene knockout approaches, we show that GflB balances the activation of Ras and Rho GTPases, which enables cells to precisely orient signaling events toward higher concentrations of chemoattractants. Furthermore, we find that GflB is located at the leading edge of migrating cells, and this localization is regulated by the actin cytoskeleton and phosphatidylserine. Our findings provide a new molecular mechanism that connects directional sensing and morphological polarization.