RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration.
RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration.
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DOI：
10.1083/jcb.200612053
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发表时间：
2007-09-24
期刊：
影响因子：
--
通讯作者：
Burridge K
中科院分区：
文献类型：
--
作者：
van Buul JD;Allingham MJ;Samson T;Meller J;Boulter E;García-Mata R;Burridge K
在跨内皮迁移（TEM）过程中，白细胞使用粘附受体，如细胞间粘附分子-1（ICAM 1）粘附到内皮。作为对这种相互作用的反应，内皮细胞抛出动态膜突起，形成部分包围粘附的白细胞的杯状物。关于调节杯子形成的信号通路知之甚少。在这项研究中，我们发现RhoG在ICAM 1参与的下游被激活。这种激活需要ICAM 1的胞内结构域。ICAM 1与RhoG共定位并结合RhoG特异性含SH3的鸟嘌呤核苷酸交换因子（SGEF）。SGEF的SH3结构域介导这种相互作用。通过小干扰RNA消耗内皮RhoG不影响白细胞粘附，但减少杯形成并抑制白细胞TEM。沉默SGEF还导致RhoG活性、杯形成和TEM的显著降低。总之，这些结果确定了一个新的信号通路，涉及RhoG和其交换因子SGEF下游的ICAM 1是至关重要的白细胞TEM。
During trans-endothelial migration (TEM), leukocytes use adhesion receptors such as intercellular adhesion molecule-1 (ICAM1) to adhere to the endothelium. In response to this interaction, the endothelium throws up dynamic membrane protrusions, forming a cup that partially surrounds the adherent leukocyte. Little is known about the signaling pathways that regulate cup formation. In this study, we show that RhoG is activated downstream from ICAM1 engagement. This activation requires the intracellular domain of ICAM1. ICAM1 colocalizes with RhoG and binds to the RhoG-specific SH3-containing guanine-nucleotide exchange factor (SGEF). The SH3 domain of SGEF mediates this interaction. Depletion of endothelial RhoG by small interfering RNA does not affect leukocyte adhesion but decreases cup formation and inhibits leukocyte TEM. Silencing SGEF also results in a substantial reduction in RhoG activity, cup formation, and TEM. Together, these results identify a new signaling pathway involving RhoG and its exchange factor SGEF downstream from ICAM1 that is critical for leukocyte TEM.
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DOI：
10.1083/jcb.200112126
发表时间：
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期刊：
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影响因子：
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