Abstract
Rho proteins operate as key regulators of the cytoskeleton, cell morphology and trafficking. Acting as molecular switches, the function of Rho GTPases is determined by guanosine triphosphate (GTP)/guanosine diphosphate (GDP) exchange and their lipidation via prenylation, allowing their binding to cellular membranes and the interaction with downstream effector proteins in close proximity to the membrane. A plethora of in vitro studies demonstrate the indispensable function of Rho proteins for cytoskeleton dynamics within different cell types. However, only in the last decades we have got access to genetically modified mouse models to decipher the intricate regulation between members of the Rho family within specific cell types in the complex in vivo situation. Translationally, alterations of the expression and/or function of Rho GTPases have been associated with several pathological conditions, such as inflammation and cancer. In the context of the GI tract, the continuous crosstalk between the host and the intestinal microbiota requires a tight regulation of the complex interaction between cellular components within the intestinal tissue. Recent studies demonstrate that Rho GTPases play important roles for the maintenance of tissue homeostasis in the gut. We will summarize the current knowledge on Rho protein function within individual cell types in the intestinal mucosa in vivo, with special focus on intestinal epithelial cells and T cells.
Highlights
(GTP)/guanosine diphosphate (GDP) exchange and their lipidation via prenylation, allowing their binding to cellular membranes and the interaction with downstream effector proteins in close proximity to the membrane
Mutations in Rho- and Racpathway related genes (DOCK2, DOCK3, PREX2, RADIL) and other somatic mutations that activate/inactivate Rho GTPases were identified in 50% Inflammatory Bowel Disease (IBD)-Colorectal Cancer (CRC), suggesting that non canonical WNT signaling can be a potential target in IBD [93]
Azathioprine response is shown in RAC1 WT IBD patients, versus patients carrying RAC11 mutations [118], and patients with active disease which respond to azathioprine therapy show decreased RAC1-guanosine triphosphate (GTP) and RAC1 expression [119], suggesting that RAC1 could be used as biomarker of azathioprine response
Summary
We can state that Rho-mediated control of the cytoskeletal function in several cell types within the gut mucosa play key roles for the maintenance of tissue homeostasis and avoid the development of local immune reactions which can lead to chronic intestinal inflammation, such as in IBD. GTPase effectors and pathways are oncogenic while others act as tumor suppressors In this context, it is important to consider the function of specific Rho GTPases and overlapping between members within the family (compensation), as well as the specificity of each individual protein in different cell types. We will summarize the current knowledge on Rho protein function within individual cell types in the intestinal mucosa in vivo, with special focus on intestinal epithelial cells and T cells, as two critical players for the maintenance of gut tissue homeostasis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
