RGS21 (Regulator of G-protein signaling 21) is a 152-amino-acid protein belonging to the R4 subfamily of RGS proteins. It functions as a GTPase-accelerating protein (GAP) for Gα subunits of heterotrimeric G proteins, modulating GPCR signaling by driving Gα into its inactive GDP-bound state . Initially identified in taste bud cells, RGS21 is expressed in sinonasal mucosa, lingual epithelium, and airway epithelial cells, where it regulates bitter taste signaling and mucociliary clearance .
RGS21 contains a single RGS domain composed of nine α-helices, sharing 64% sequence identity with RGS2 . Key structural features include:
Recombinant RGS21 includes a 24-amino-acid His-tag for purification and retains functional activity in biochemical assays .
RGS21 negatively regulates GPCR signaling by stabilizing the transition state of Gα during GTP hydrolysis. Key findings:
RGS21 binds and accelerates GTP hydrolysis on:
Gα Subunit | Binding Affinity | GAP Activity | Source |
---|---|---|---|
Gαi1 | High | Accelerates GTPase | |
Gαq | Moderate | Modulates signaling |
Overexpression in 16HBE airway cells reduces bitterant-induced cAMP and calcium flux .
Knockdown enhances bitter taste responsiveness, confirming its role as a negative regulator .
RGS21 is selectively expressed in:
Taste Buds: Co-localized with bitter (T2R) and sweet (T1R2/T1R3) taste receptors, α-gustducin, and PLCβ2 .
Sinonasal Mucosa: Detected via qRT-PCR and transgenic RFP reporter mice .
Airway Epithelium: Critical for mucociliary clearance regulation .
Mucociliary Clearance: May enhance airway defense by regulating bitterant-induced cilia beat .
Taste Regulation: Modulates bitter/sweet perception via Gαi/q pathways .
Physiological Function: Direct in vivo evidence for mucociliary or taste roles remains limited.
Therapeutic Targets: RGS21 inhibition may enhance bitterant-mediated airway clearance.
Regulator of G-protein signaling 21, RGS21.
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The Regulator of G-Protein Signaling 21 (RGS21) 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 pathways are essential for various physiological processes, including sensory perception, immune responses, and neurotransmission.
The RGS21 gene is located on chromosome 1 and encodes a protein that consists of 176 amino acids . The human recombinant form of RGS21 is produced in E. coli and is a single, non-glycosylated polypeptide chain with a molecular mass of approximately 20.2 kDa . This recombinant protein is often fused with a His-tag at the N-terminus to facilitate purification through chromatographic techniques .
RGS21 functions as a GTPase-activating protein (GAP) for Gα subunits of heterotrimeric G proteins. By accelerating the hydrolysis of GTP to GDP, RGS21 effectively terminates the signaling initiated by GPCRs . This regulation is vital for maintaining the balance and proper functioning of cellular signaling networks.
Dysregulation of RGS proteins, including RGS21, has been implicated in various diseases. For instance, alterations in RGS21 expression have been associated with certain types of cancers . The protein’s ability to modulate GPCR signaling makes it a potential target for therapeutic interventions aimed at treating diseases characterized by aberrant GPCR activity.
The study of RGS21 and other RGS proteins continues to be an area of active research. Understanding the precise mechanisms by which RGS21 regulates GPCR signaling can provide insights into the development of novel therapeutic strategies. The recombinant form of RGS21 is particularly useful in research settings, allowing scientists to study its function and interactions in a controlled environment.