Rho Family of GTPases - Regulators

Regulators

Three general classes of regulators of rho protein signaling have been identified: guanine nucleotide exchange factor (GEFs), GTPase-activating proteins (GAPs) and guanine nucleotide dissociation inhibitors (GDIs). GEFs activate Rho proteins by catalyzing the exchange of GDP for GTP. GAPs control the ability of the GTPase to hydrolyze GTP to GDP, controlling the natural rate of movement from the active conformation to the inactive conformation. GDI proteins form a large complex with the rho protein helping to prevent diffusion within the membrane and into the cytosol, thus acting as an anchor and allowing for very specific spatial control of rho activation.

Recent works have unveiled important additional regulatory mechanisms: microRNA (miRNA) regulating post-transcriptional processing of Rho GTPase-encoding mRNAs; palmitoylation and nuclear targeting affecting intracellular distribution; post-translational phosphorylation, transglutamination and AMPylation impacting Rho GTPase signaling; and ubiquitination controlling Rho GTPase protein stability and turnover. These modes of regulation add to the complexity of the Rho GTPase signaling network and allow precise spatiotemporal control of individual Rho GTPases.

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