Abstract
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.
Highlights
We focus on the function of Trio signaling for the regulation of endothelial cell morphology and endothelial barrier function
In this in the healthy endothelium and how Trio may be deregulated in vascular-related inflamreview, we focus on the function of Trio signaling in the healthy endothelium and how Trio matory diseases
We can conclude that endothelial Trio is required for junction stabilization through the local activation of Rac1; it is essential for proper vascular barrier integrity
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Isoforms of Trio can be formed due to alternative splicing (Figure 1). These isoforms, proof is necessary confirm deny this claim. TrioA-E, have beento detected inor different parts of theIsoforms brain and of be either one or both alternative splicing These isoforms, TrioA-E, have been detected in different of the GEF domains [13,14,15]. Full length Trio is ubiqDifferences in Trio isoform expression might play a role in the regulation of Rac and RhoA uitously expressed in the endothelium of all organs [16]. Compared to VE-cadherin (an endothelial cell marker), Trio expression is function of Trio has appeared essential for the regulation of endothelial cell morphology relatively low in all organs.
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