Gene Number: 5997

Location: 1q31.2

Key Functions: GTPase-activating protein activity for Gα subunits, negative regulation of GPCR signaling, vascular smooth muscle tone, neuronal signaling modulation, stress and anxiety response

RGS2 encodes the Regulator of G-protein Signaling 2, which is an essential member of the RGS protein family. This family of proteins plays a crucial role in the regulation of G-protein-coupled receptor (GPCR) signaling pathways by accelerating the hydrolysis of GTP (guanosine triphosphate) on activated Gα subunits. This action effectively terminates the signaling cascade initiated by GPCR activation, thereby ensuring that cellular responses are tightly controlled and appropriately timed. The regulation of GPCR signaling is vital for numerous physiological processes, making RGS2 a key player in maintaining cellular homeostasis.

RGS2 is highly expressed in:

• Vascular smooth muscle cells

• The heart

• Several brain regions, where it modulates vasoconstriction, cardiac function, and neuronal excitability. In vascular smooth muscle cells, RGS2 plays a pivotal role in regulating the tone of blood vessels, thus influencing blood pressure. In the heart, it helps to fine-tune cardiac contractility and rhythm. Furthermore, in various brain regions, RGS2 is involved in modulating neuronal excitability and synaptic transmission, which are critical for normal cognitive functions and emotional responses. By dampening GPCR pathways, RGS2 aids in maintaining blood pressure homeostasis and significantly influences behavioral responses to stress, thereby contributing to the overall balance of the cardiovascular and nervous systems.

Mutations or dysregulation of RGS2 have been linked to a range of pathological conditions, including hypertension, heart failure, and anxiety disorders. Research indicates that reduced expression or impaired activity of RGS2 can lead to prolonged GPCR signaling, which in turn contributes to elevated vascular tone and increased peripheral resistance, often resulting in hypertension. Additionally, the maladaptive remodeling of cardiac tissue can occur, leading to heart failure due to the heart's inability to cope with increased workload. In the context of anxiety disorders, altered RGS2 expression has been associated with changes in stress-related behaviors, suggesting that RGS2 may play a role in how individuals respond to stress and anxiety-inducing stimuli. The multifaceted roles of RGS2 highlight its importance in both cardiovascular health and mental well-being, making it a significant focus of ongoing research aimed at understanding its contributions to these complex conditions.