Temperature sensing by the calcium-sensing receptor

Frontiers in Physiology

Physiology

Hee-chang Mun¹  Leigh Delbridge²  Philip W. Kuchel³  Sarah C. Brennan⁴  Arthur D. Conigrave⁴ 

[1] Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia;Department of Surgery, Mater Hospital, North Sydney, NSW, Australia;School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia;School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Sydney, NSW, Australia;Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia;

关键词: calcium sensing receptor;    temperature sensing;    intracellular calcium oscillations;    protein kinase C;    protein phosphatase;    GPCR;   

DOI  :  10.3389/fphys.2023.1117352

 received in 2022-12-06, accepted in 2023-01-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

Whether GPCRs support the sensing of temperature as well as other chemical and physical modalities is not well understood.Introduction: Extracellular Ca2+ concentration (Ca2+o) modulates core body temperature and the firing rates of temperature-sensitive CNS neurons, and hypocalcemia provokes childhood seizures. However, it is not known whether these phenomena are mediated by Ca2+o-sensing GPCRs, including the calcium-sensing receptor (CaSR). In favor of the hypothesis, CaSRs are expressed in hypothalamic regions that support core temperature regulation, and autosomal dominant hypocalcemia, due to CaSR activating mutations, is associated with childhood seizures.Methods: Herein, we tested whether CaSR-dependent signaling is temperature sensitive using an established model system, CaSR-expressing HEK-293 cells.Results: We found that the frequency of Ca2+o-induced Ca2+i oscillations but not the integrated response was linearly dependent on temperature in a pathophysiologically relevant range. Chimeric receptor analysis showed that the receptor’s C-terminus is required for temperature-dependent modulation and experiments with the PKC inhibitor GF109203X and CaSR mutants T888A and T888M, which eliminate a key phosphorylation site, demonstrated the importance of repetitive phosphorylation and dephosphorylation.Discussion and Conclusion: CaSRs mediate temperature-sensing and the mechanism, dependent upon repetitive phosphorylation and dephosphorylation, suggests that GPCRs more generally contribute to temperature-sensing.

【 授权许可】

Unknown   
Copyright © 2023 Brennan, Mun, Delbridge, Kuchel and Conigrave.