Senoo Hiroshi, Cai Huaqing, Wang Yu, Sesaki Hiromi, Iijima Miho
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205 State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Mol Biol Cell. 2016 May 15;27(10):1596-605. doi: 10.1091/mbc.E15-11-0796. Epub 2016 Mar 23.
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.
方向感知是细胞将外部化学梯度转化为内部信号事件的过程，在趋化作用中至关重要。我们之前表明，一种Rho GTP酶RacE调节盘基网柄菌细胞中的梯度感知。在此，我们利用亲和纯化和质谱技术鉴定出一种新型的RacE结合蛋白GflB，它含有一个Ras鸟苷酸交换因子（GEF）结构域和一个Rho GTP酶激活蛋白（GAP）结构域。通过生化和基因敲除方法，我们表明GflB平衡了Ras和Rho GTP酶的激活，使细胞能够将信号事件精确地导向更高浓度的趋化因子。此外，我们发现GflB位于迁移细胞的前沿，这种定位受肌动蛋白细胞骨架和磷脂酰丝氨酸的调节。我们的发现提供了一种连接方向感知和形态极化的新分子机制。
