Functional and Therapeutic Relevance of Rho GTPases in Innate Immune Cell Migration and Function during Inflammation: An In Silico Perspective

Figure 1

Overview of activation and regulation of Rho proteins during inflammation. Extracellular signals mediated through cell surface receptors such as GPCR, integrins, and cytokine receptors lead to the activation of RhoGTPases, resulting in various effector functions of inflammatory immune cells. The precise regulation of Rho proteins is performed by mostly three regulatory proteins, namely, GEFs, GAPs, and GDIs. Rho proteins primarily active in GTP-bound form become nonfunctional in GDP-bound form. Guanine Nucleotide Exchange Factors (GEFs) activate the Rho proteins by exchanging GDP for GTP, and in GTP-activated form, GTPases bind to different effectors and perform a downstream cellular function such as actin cytoskeleton rearrangement, cell cycle progression, and gene expression. GTPase-Activating Proteins (GAPs) enhance the intrinsic GTP hydrolysis of Rho-GTPase by releasing inorganic phosphate (Pi), thereby inactivating GTPases. The third regulatory protein is guanine nucleotide dissociation inhibitors (GDIs), which keep Rho proteins in GDP-bound form and prevent the localization of GTPases from the cytosol to the plasma membrane, and protects them from the action of GEFs.