Loss of the Nutrient Sensor Tas1R3 Leads to Reduced Bone Resorption
Medicine and Health Sciences
The taste receptor type 1 (TAS1R) family of heterotrimeric G protein-coupled receptors participates in monitoring energy and nutrient status. TAS1R member 3 (TAS1R3) is a bi-functional protein that recognizes amino acids such as L-glycine and L-glutamate or sweet molecules such as sucrose and fructose when dimerized with TAS1R member 1 (TAS1R1) or TAS1R member 2 (TAS1R2), respectively. Loss of TAS1R3 expression causes impaired mTORC1 signaling and increased autophagy, indicating that signaling through this receptor is critical for assessing nutrient needs. It was recently reported that deletion of TAS1R3 expression in Tas1R3 mutant mice leads to increased cortical bone mass and trabecular remodeling, but the underlying cellular mechanism leading to this phenotype remains unclear. The cellular mechanism of the increased bone mass was investigated by independently confirming that TAS1R family members are natively expressed in bone and that Tas1R3 mutant mice exhibit high bone mass. Cells of the bone-forming lineage in vitro express Tas1R family members, but levels of the bone formation marker Procollagen Type I N-terminal Propeptide are unchanged in the serum of 20-week-old Tas1R3 mutant mice as compared to controls. In contrast, levels of the bone resorption marker Collagen Type I C-telopeptide are reduced greater than 60% in Tas1R3 mutant mice. Consistent with this, Tas1R3 and Tas1R2 are expressed in primary osteoclasts and their expression levels positively correlate with differentiation status. Collectively, these findings suggest that high bone mass in Tas1R3 mutant mice is due to uncoupled bone remodeling with reduced osteoclast function and provide rationale for future experiments examining the cell type-dependent role for TAS1R family members in nutrient sensing in postnatal bone remodeling.
Copyright all authors
Ward, Taylor OMSII, "Loss of the Nutrient Sensor Tas1R3 Leads to Reduced Bone Resorption" (2016). MU-COM Research Day. 25.