The novel RacE-binding protein GflB sharpens Ras activity at the leading edge of migrating cells

Hiroshi Senoo; Huaqing Cai; Yu Wang; Hiromi Sesaki; Miho Iijima

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The novel RacE-binding protein GflB sharpens Ras activity at the leading edge of migrating cells

机译：新型RacE结合蛋白GflB在迁移细胞的前沿增强了Ras活性

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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.

机译：定向感测是细胞趋化性中必不可少的过程，其中细胞将外部化学梯度转化为内部信号事件。我们先前显示，Rho GTPase RacE调节Dictyostelium细胞中的梯度感测。在这里，使用亲和纯化和质谱，我们确定了一种新型的RacE结合蛋白GflB，其中包含Ras GEF域和Rho GAP域。使用生化和基因敲除方法，我们表明GflB平衡了Ras和Rho GTPases的激活，这使细胞能够将信号事件精确地定向到趋向于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，并且该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新的分子机制，将方向感应和形态极化联系在一起。

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《Molecular biology of the cell》 |2016年第10期|共10页
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Hiroshi Senoo; Huaqing Cai; Yu Wang; Hiromi Sesaki; Miho Iijima;
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1. The novel RacE-binding protein GflB sharpens Ras activity at the leading edge of migrating cells [J] . Senoo Hiroshi, Cai Huaqing, Wang Yu, Molecular biology of the cell . 2016,第10期

机译：新型RacE结合蛋白GflB在迁移细胞的前沿增强了Ras活性
2. Recruitment and activation of SLK at the leading edge of migrating cells requires Src family kinase activity and the LIM-only protein 4 [J] . Baron Kyla D., Al-Zahrani Khalid, Conway Jillian, Biochimica et biophysica acta. Molecular cell research . 2015,第7期

机译：在迁移细胞的前沿招募和激活SLK需要Src家族激酶活性和仅LIM蛋白4
3. Recruitment and activation of SLK at the leading edge of migrating cells requires Src family kinase activity and the LIM-only protein 4 (vol 1853, pg 1683, 2015) [J] . Baron Kyla D., Al-Zahrani Khalid, Conway Jillian, Biochimica et biophysica acta. Molecular cell research . 2015,第10aPta1期

机译：在迁移细胞的前沿招募和激活SLK需要Src家族激酶活性和LIM-only蛋白4（vol 1853，pg 1683，2015）
4. BI HEX~(TM) - Platform for Fast Track Generation of High Producer Cell Lines Leading to High-Titer Processes for Production of Therapeutic Proteins from Mammalian Cells [C] . Torsten W. Schulz, Stefan Schlatter, Hitto Kaufmann, European Society of Animal Cell Technology . 2010

机译：BI Hex〜（TM） - 快速轨道生成高生产电平细胞系的平台，导致来自哺乳动物细胞的治疗蛋白质的高滴度工艺
5. Vesicle trafficking and protein synthesis, target adenylyl cyclase A to the back of migrating cells, localizing the release of chemoattractant to the trailing edge. [D] . Kriebel, Paul W. 2009

机译：囊泡运输和蛋白质合成，将腺苷酸环化酶A靶向到迁移细胞的后部，将趋化因子的释放定位在后缘。
6. Corrigendum to “Recruitment and activation of SLK at the leading edge of migrating cells requires Src family kinase activity and the LIM-only protein 4” Biochim. Biophys. Acta 1853/7 (2015) 1683–1692 [O] . Baron Kyla D., Al-Zahrani Khalid, Conway Jillian, 2015

机译：“在迁移细胞的前沿招募和激活SLK需要Src家族激酶活性和仅LIM蛋白4”的更正Biochim。生物物理学。 Act 1853/7（2015）1683–1692
7. Cellular Regulation of ADP-Ribosylation of Proteins. 4. Conversion of Poly(ADP-Ribose) Polymerase Activity to NAD-Glycohydrolase during Retinoic Acid-Induced Differentiation of HL60 Cells [R] . Kirsten, E., Bauer, P. I., Kun, E. 1991

机译：蛋白质aDp-核糖基化的细胞调节。 4.维甲酸诱导HL60细胞分化过程中聚（aDp-核糖）聚合酶活性转化为NaD-糖水解酶

The novel RacE-binding protein GflB sharpens Ras activity at the leading edge of migrating cells

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