Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan 23;9(1):24.
doi: 10.1038/s41420-023-01329-w.

Role of Rho GTPases in inflammatory bowel disease

Xiaoling Li #  1 , Mudan Zhang #  1 , Gaoshi Zhou #  1 , Zhuo Xie  1 , Ying Wang  1 , Jing Han  1 , Li Li  1 , Qirui Wu  1 , Shenghong Zhang #  2
Affiliations
Review

Role of Rho GTPases in inflammatory bowel disease

Xiaoling Li et al. Cell Death Discov. .

Abstract

Rat sarcoma virus homolog (Rho) guanosine triphosphatases (GTPases) function as "molecular switch" in cellular signaling regulation processes and are associated with the pathogenesis of inflammatory bowel disease (IBD). This chronic intestinal tract inflammation primarily encompasses two diseases: Crohn's disease and ulcerative colitis. The pathogenesis of IBD is complex and considered to include four main factors and their interactions: genetics, intestinal microbiota, immune system, and environment. Recently, several novel pathogenic components have been identified. In addition, potential therapies for IBD targeting Rho GTPases have emerged and proven to be clinically effective. This review mainly focuses on Rho GTPases and their possible mechanisms in IBD pathogenesis. The therapeutic possibility of Rho GTPases is also discussed.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Schematic diagram of Rho GTPases molecular switches and its regulators.
Rho GTPases are members of the Ras superfamily, acting as molecular switches and consisting of inactive GDP-bound and active GTP-bound forms. In the inactive GDP-bound form, GEFs promote the activation of Rho GTPases by replacing GDP with GTP, thus Rho GTPases change its conformation and can bind and activate various downstream effectors in order to trigger multiple cellular functions. By contrast, GAPs increase the hydrolysis of GTP to GDP and inhibit the activation of Rho GTPases. GDIs interacts with the GDP-bound Rho GTPases, preventing its localization to the cell membrane and maintaining Rho GTPases in the inactive form. When GDIs released, GDP-bound Rho GTPases will anchor to the cell membrane and be further activated by binding to GEFs. GEFs guanine nucleotide exchange factors, GAPs GTPase-activating proteins, GDIs guanine nucleotide dissociation inhibitors.
Fig. 2
Fig. 2. Role of Rho GTPases in the adaptive immune system.
Abnormal T cells activation, accumulation, differentiation of different T cells subsets and inappropriate apoptosis are linked to IBD immunopathogenesis. Rho GTPases are involved in T cells basic functions. Migration of T cell initiates with enhanced adhension mediated by Rac and RhoA, the former also participates in lymphocyte homing. Cdc42, Rac and RhoA regulate T cell movement with different mechanisms. Effective T cell activation requires stable conjunction between T cell and APC and the signaling transduction. RhoA and Rac contribute to both the process while Cdc42 enhances the former process and inhibits the latter. RhoH and RhoG are also involved in signaling transduction, mainly exerting a positive and negative function, respectively. Rho GTPases also help lymphocytes differentiate into diverse effector or regulatory T cell subsets to participate in inflammatory and anti-inflammatory processes. Cdc42, Rac and RhoA are involved in the Fas/FasL induced apoptosis of T cell, both in the induction and late stage. WASp Wiskott-Aldrich syndrome protein, Arp2/3 actin-related protein 2/3, IS immunological synapse, ERM protein ezrin-radixin-moesin protein, JNK c-jun N-terminal kinase, AP-1 activate protein-1, NFAT nuclear factor of activated T cells, NF-κB nuclear factor of kappa B, IL-12 interluekin-12.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Agrawal M, Spencer EA, Colombel JF, Ungaro RC. Approach to the Management of Recently Diagnosed Inflammatory Bowel Disease Patients: A User’s Guide for Adult and Pediatric Gastroenterologists[J/OL] Gastroenterology. 2021;161:47–65. doi: 10.1053/j.gastro.2021.04.063. - DOI - PMC - PubMed
    1. De Souza HSP, Fiocchi C. Immunopathogenesis of IBD: current state of the art[J/OL] Nat Rev Gastroenterol Hepatol. 2016;13:13–27. doi: 10.1038/nrgastro.2015.186. - DOI - PubMed
    1. Jaffe AB, Hall A. Rho GTPases: biochemistry and biology[J/OL] Annu Rev Cell Dev Biol. 2005;21:247–69. doi: 10.1146/annurev.cellbio.21.020604.150721. - DOI - PubMed
    1. Hodge RG, Ridley AJ. Regulating Rho GTPases and their regulators[J/OL] Nat Rev Mol Cell Biol. 2016;17:496–510. doi: 10.1038/nrm.2016.67. - DOI - PubMed
    1. Hall A. Rho GTPases and the actin cytoskeleton[J/OL] Science. 1998;279:509–14. doi: 10.1126/science.279.5350.509. - DOI - PubMed