RGS21, a regulator of taste and mucociliary clearance?

Laryngoscope. 2014 Mar;124(3):E56-63. doi: 10.1002/lary.24326. Epub 2013 Oct 2.


Objectives/hypothesis: Motile cilia of airway epithelial cells help to expel harmful inhaled material. Activation of bitterant-responsive G protein-coupled receptors (GPCRs) is believed to potentiate cilia beat frequency and mucociliary clearance. In this study, we investigated whether regulator of G protein signaling-21 (RGS21) has the potential to modulate signaling pathways connected to airway mucociliary clearance, given that RGS proteins modulate GPCR signaling by acting as GTPase-accelerating proteins (GAPs) for the Gα subunits of heterotrimeric G proteins.

Study design: This is a pilot investigation to determine if RGS21, a potential tastant specific RGS gene, is expressed in sinonasal mucosa, and to determine its specific Gα substrate using in vitro biochemical assays with purified proteins.

Methods: Rgs21 expression in sinonasal mucosa was determined using quantitative, real-time PCR and a transgenic mouse expressing RFP from the Rgs21 promoter. Rgs21 was cloned, over-expressed, and purified using multistep protein chromatography. Biochemical and biophysical assays were used to determine if RGS21 could bind and accelerate the hydrolysis of GTP on heterotrimeric Gα subunits.

Results: Rgs21 was expressed in sinonasal mucosa and lingual epithelium. Purified recombinant protein directly bound and accelerated GTP hydrolysis on Gα subunits.

Conclusions: Rgs21 is expressed in sinonasal mucosa, is amenable to purification as a recombinant protein, and can bind to Gα(i/o/q) subunits. Furthermore, RGS21 can accelerate the hydrolysis rate of GTP on Gαi subunits. This provides evidence that RGS21 may be a negative regulator of bitterant responses. Future studies will be needed to determine the physiological role of this protein in mucociliary clearance.

Keywords: G proteins; Regulators of G protein signaling (RGS); gustation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Gene Expression Regulation*
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Mucociliary Clearance / genetics*
  • Pilot Projects
  • RGS Proteins / genetics*
  • Random Allocation
  • Real-Time Polymerase Chain Reaction / methods
  • Sensitivity and Specificity
  • Signal Transduction / genetics
  • Taste / genetics*


  • RGS Proteins