Calcium-Sensing GPCR Assays
Background of Calcium-Sensing Receptor
Calcium signaling exerts an essential impact on multiple cellular functions. Calcium-sensing receptor (CASR) is a highly complex GPCR closely associated with the control of parathyroid hormone (PTH) and the maintenance of calcium homeostasis. Briefly, minor alters in the extracellular concentration of Ca2+ can be monitored by aberrant CASR in the parathyroid glands, which then precisely regulate PTH secretion through Ca2+ reabsorption.
Vital Roles of CASR
Abnormal expression levels and receptor activities of CASR have been involved in many disorders, including neonatal severe hyperparathyroidism (NSHPT), familial hypocalciuric hypercalcemia type 1 (FHH1), autosomal dominant hypocalcemia type 1 (ADH1) and asthma. What is more, there is growing evidence revealing that CASR participates in various biological processes not related to calcium homeostasis.
Fig.1. The overall structure of full-length CASR. (Wen, 2021)
Mechanism of Adenosine Receptors
CASR is a complex GPCR with multiple binding sites and many physiological roles. In addition, CASR responds to a variety of stimuli, such as amino acids, peptides, cations, and polyamines. The following table summarizes information about its main agonists, antagonists, as well as mechanisms.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| Calcium-Sensing Receptor | CASR |
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Assay List of Calcium Sensor Receptor
Creative Biolabs can provide a range of assays of calcium sensor receptor. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Calcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis |
| Journal | Nature Communications |
| Published | 2020 |
| Abstract | CASR has been demonstrated to induce NLRP3 inflammasome activation in vivo and in vitro. Increased calcium also triggers constitutive macropinocytosis in monocytes and macrophages through G protein-mediated CASR signaling. CASR is found in various cell types. Furthermore, CASR induces an inflammatory response in allergic asthma, myocardial infarction, and obesity. In rheumatoid arthritis (RA), increased CASR expression is closely associated with severe coronary calcification, but the mechanism of CASR's role in arthritis is currently unclear. |
| Result |
Increased extracellular calcium concentration activates the NLRP3 inflammasome in monocytes through CASR. The serum protein fetuin-A stabilizes calcium and phosphate into colloidal calcin particles (CPP) to prevent extraosseous calcification in vivo, experimental results revealed that monocytes phagocytosed CPP by macropinocytosis, and this process was associated with increased calcium-induced CASR signaling. Enhanced macropinocytosis by CPPs favored increased lysosomal activity, NLRP3 inflammasome activation, and IL-1β release. Monocytes in the context of RA contributed to CPP uptake and IL-1β release in response to CASR signaling. Therefore, researchers proposed that CASR-mediated NLRP3 inflammasome activation not only benefited inflammatory arthritis and systemic inflammation in RA, but may also played a role in other inflammatory conditions. Inhibition of CASR-mediated CPP uptake provided a new idea for the treatment of RA.
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Fig.2. Extracellular calcium-mediated calciprotein particle uptake mediates inflammasome activation. (Jäger, 2020)
References
- Wen, T.; et al. Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor. Science Advances. 2019; 7(23): eabg1483.
- Jäger, E.; et al. Calcium-sensing receptor-mediated NLRP3 inflammasome response to calciprotein particles drives inflammation in rheumatoid arthritis. Nature communications. 2020; 11(1): 1-17.
