Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Communications Biology Année : 2024

Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges

Résumé

G protein-coupled receptors naturally oscillate between inactive and active states, often resulting in receptor constitutive activity with important physiological consequences. Among the class C G protein-coupled receptors that typically sense amino-acids and their derivatives, the calcium sensing receptor (CaSR) tightly controls blood calcium levels. Its constitutive activity has not yet been studied. Here, we demonstrate the importance of the inter-subunit disulfide bridges in maintaining the inactive state of CaSR, resulting in undetectable constitutive activity, unlike the other class C receptors. Deletion of these disulfide bridges results in strong constitutive activity that is abolished by mutations preventing amino acid binding. It shows that this inter-subunit disulfide link is necessary to limit the agonist effect of amino acids on CaSR. Furthermore, human genetic mutations deleting these bridges and associated with hypocalcemia result in elevated CaSR constitutive activity. These results highlight the physiological importance of fine tuning the constitutive activity of G protein-coupled receptors.
Fichier principal
Vignette du fichier
Ma et al CaSR Ca-SS CommBiol24.pdf (12.25 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-04569775 , version 1 (08-05-2024)

Identifiants

Citer

Shumin Ma, Xueliang Yin, Jean-Philippe Pin, Philippe Rondard, Ping Yi, et al.. Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges. Communications Biology, 2024, 7 (1), pp.501. ⟨10.1038/s42003-024-06189-3⟩. ⟨hal-04569775⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More