Regulator of G-Protein Signaling 4 (RGS4) is a member of the RGS protein family, which plays a crucial role in the modulation of G-protein coupled receptor (GPCR) signaling pathways. These proteins act as GTPase-activating proteins (GAPs) for G alpha subunits of heterotrimeric G proteins, driving them into their inactive GDP-bound forms . RGS4 is encoded by the RGS4 gene located on chromosome 1q23.3 in humans .
RGS4 is involved in the regulation of various physiological processes by modulating the signaling amplitude and duration of GPCR pathways. It deactivates G protein subunits of the Gi alpha, Go alpha, and Gq alpha subtypes . This regulation is essential for maintaining cellular homeostasis and responding to external stimuli.
RGS4 is predominantly expressed in the nervous system, particularly in regions such as the middle temporal gyrus, frontal pole, and prefrontal cortex . It is also found in other tissues, including the heart, where it plays a role in protecting against atrial fibrillation via calcium signaling attenuation .
Human recombinant RGS4 is typically produced using recombinant DNA technology. The gene encoding RGS4 is cloned into an expression vector, which is then introduced into a suitable host cell, such as Escherichia coli or mammalian cells. The host cells express the RGS4 protein, which is subsequently purified using techniques such as affinity chromatography.
RGS4 interacts with G alpha subunits of heterotrimeric G proteins, accelerating their intrinsic GTPase activity. This interaction leads to the hydrolysis of GTP to GDP, thereby inactivating the G protein and terminating the signal transduction . The activity of RGS4 can be analyzed using various biochemical assays, including GTPase activity assays and protein-protein interaction studies.
RGS4 has been implicated in several neurological disorders, including schizophrenia and Parkinson’s disease . Its role in modulating GPCR signaling pathways makes it a potential therapeutic target for these conditions. Additionally, RGS4’s involvement in cardiac function highlights its importance in cardiovascular research .