ARHGEF18

Last update 08 May 2025

Basic Info

Synonyms

114 kDa Rho-specific guanine nucleotide exchange factor, ARHGEF18, KIAA0521

+ [8]

Introduction

Acts as a guanine nucleotide exchange factor (GEF) for RhoA GTPases. Its activation induces formation of actin stress fibers. Also acts as a GEF for RAC1, inducing production of reactive oxygen species (ROS). Does not act as a GEF for CDC42. The G protein beta-gamma (Gbetagamma) subunits of heterotrimeric G proteins act as activators, explaining the integrated effects of LPA and other G-protein coupled receptor agonists on actin stress fiber formation, cell shape change and ROS production. Required for EPB41L4B-mediated regulation of the circumferential actomyosin belt in epithelial cells (PubMed:22006950).

100 Clinical Results associated with ARHGEF18

100 Translational Medicine associated with ARHGEF18

0 Patents (Medical) associated with ARHGEF18

Literatures (Medical) associated with ARHGEF18

01 Mar 2025·Cell Reports

ARHGEF18 is a flow-responsive exchange factor controlling endothelial tight junctions and vascular leakage

Article

Author: Le Ruz, Robin ; Baron-Menguy, Céline ; Rio, Marc ; Babahnini, Ibtissam ; Loirand, Gervaise ; Moutaoukil, Reda ; Bodet, Maxence ; Lebot, Corentin ; Vion, Anne-Clémence ; Batta, Surya Prakash Rao

The shear stress resulting from blood flow is a major regulator of endothelial cell (EC) biology and morphology. Rho protein-mediated cytoskeleton remodeling is an early and essential step of EC responses to flow. However, how Rho protein signaling is controlled by shear stress remains unclear. Here we demonstrate that phosphorylation, activity, and expression of the Rho nucleotide exchange factor (RhoGEF) ARHGEF18 in ECs are modulated by the magnitude of shear stress. When phosphorylated, ARHGEF18 interacts with tight junctions; participates in EC elongation, alignment, and migration; and allows the maintenance of the endothelial barrier under physiological flow conditions. In mice, ARHGEF18 is involved in tight junction formation, flow response of ECs, and the control of vascular permeability. Together, our results identified ARHGEF18 as the first flow-sensitive RhoGEF in ECs, whose activity is essential for the maintenance of intercellular junctions and the control of vascular permeability in vivo.

01 Mar 2025·Disease Models & Mechanisms

Establishment and functional studies of a model of cardiomyopathy with cardiomyocyte-specific conditional knockout of Arhgef18

Article

Author: Yuan, Wenjing ; Wan, Kun ; Lu, Tiewei ; Fu, Xiaoqiong ; Pan, Bo ; Li, Jiajin ; Ge, Mei

ABSTRACTThe rising incidence of cardiomyopathies poses a significant threat to the physical and mental health of patients. The establishment of an animal model that accurately reflects the clinicopathological characteristics of cardiomyopathy is essential for investigating its pathogenesis. In this study, a cardiomyocyte-specific Arhgef18 conditional knockout (cKO) mouse model was established with Cre/LoxP technology, and the results confirmed that the protein encoded by Arhgef18 (Rho/Rac guanine nucleotide exchange factor 18) was knocked out effectively in the myocardium of Arhgef18flox/flox; Nkx2.5-Cre (Arhgef18fl/fl cKO) mice. Compared to Arhgef18fl/fl mice, Arhgef18fl/fl cKO mice presented with slower body weight growth and no differences in survival curves. Cardiac structure and function revealed that Arhgef18fl/fl cKO mice developed biventricular enlargement, ventricular wall thinning and left-ventricular systolic dysfunction, along with increased Nppa and Nppb mRNA expression levels. Additionally, Arhgef18fl/fl cKO mice showed cardiomyocyte cytoskeletal rearrangements and cell polarity disorders. Our study results suggest that Arhgef18 cKO mice could provide an ideal animal model for the genetic investigation of cardiomyopathy.

01 Apr 2024·Veterinary Microbiology

ARHGEF18 can promote BVDV NS5B activation of the host NF-κB signaling pathway by combining with the NS5B-palm domain

Article

Author: Yin, Jiying ; Ma, Shuqi ; Zhou, Zehui ; Wang, Xiaonan ; Diao, Naichao ; Shi, Kun ; Du, Rui ; Zhou, Hongming ; Wang, Qi ; Tian, Tian ; He, Ning ; Jia, Wenyi

Rho guanine nucleotide exchange factor 18 (ARHGEF18) is a member of the Rho guanine nucleotide exchange factor (RhoGEF) family. RhoGEF plays an important role in the occurrence of tumors and neurological diseases; however, its involvement in host cell resistance against pathogenic microorganisms is mostly unknown. Herein, we report that bovine viral diarrhea virus (BVDV) nonstructural protein 5B (NS5B) can activate the nuclear factor kappa B (NF-κB) signaling pathway to induce an immune response. To clarify the functional domains of NS5B that activate NF-κB signaling, the six structural domains of NS5B were expressed separately: NS5B-core, NS5B-finger, NS5B-palm, NS5B-thumb, NS5B-N and NS5B-c domain. We preliminarily determined that the functional domains of NS5B that activate NF-κB signaling are the finger and palm domains. We used a bovine kidney cell cDNA library and yeast two-hybrid technology to identify that the host protein ARHGEF18 interacts with NS5B. Co-immunoprecipitation assays showed that ARHGEF18 interacts strongly with NS5B-palm. Interestingly ARHGEF18 could promote NF-κB signaling activation by BVDV NS5B. In addition silencing ARHGEF18 significantly inhibited NS5B-palm activation of NF-κB signaling. We concluded that ARHGEF18 can bind to BVDV NS5B through the palm domain to activate the NF-κB pathway. These findings provide direct evidence that BVDV NS5B induces immune responses by activating NF-κB signaling.

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ARHGEF18

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