Laboratory for Vascular Cell Biology, Department of Molecular Hematology, Sanquin Research, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands.
Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1066 CX Amsterdam, The Netherlands.
Int J Mol Sci. 2021 Sep 21;22(18):10168. doi: 10.3390/ijms221810168.
Many cellular processes are controlled by small GTPases, which can be activated by guanine nucleotide exchange factors (GEFs). The RhoGEF Trio contains two GEF domains that differentially activate the small GTPases such as Rac1/RhoG and RhoA. These small RhoGTPases are mainly involved in the remodeling of the actin cytoskeleton. In the endothelium, they regulate junctional stabilization and play a crucial role in angiogenesis and endothelial barrier integrity. Multiple extracellular signals originating from different vascular processes can influence the activity of Trio and thereby the regulation of the forementioned small GTPases and actin cytoskeleton. This review elucidates how various signals regulate Trio in a distinct manner, resulting in different functional outcomes that are crucial for endothelial cell function in response to inflammation.
许多细胞过程受小分子 GTP 酶控制，这些小分子 GTP 酶可被鸟嘌呤核苷酸交换因子（GEFs）激活。RhoGEF Trio 包含两个 GEF 结构域，可差异化激活 Rac1/RhoG 和 RhoA 等小分子 GTP 酶。这些小分子 RhoGTP 酶主要参与肌动蛋白细胞骨架的重塑。在血管内皮细胞中，它们调节连接的稳定性，在血管生成和内皮屏障完整性中发挥关键作用。来自不同血管过程的多种细胞外信号可影响 Trio 的活性，从而调节上述小分子 GTP 酶和肌动蛋白细胞骨架。本综述阐述了各种信号如何以不同的方式调节 Trio，从而产生不同的功能结果，这些结果对于内皮细胞在炎症反应中发挥功能至关重要。
