Absence of calcium-sensing receptor basal activity due to inter-subunit disulfide bridges.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
25 Apr 2024
25 Apr 2024
Historique:
received:
21
08
2023
accepted:
12
04
2024
medline:
26
4
2024
pubmed:
26
4
2024
entrez:
25
4
2024
Statut:
epublish
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.
Identifiants
pubmed: 38664468
doi: 10.1038/s42003-024-06189-3
pii: 10.1038/s42003-024-06189-3
doi:
Substances chimiques
Receptors, Calcium-Sensing
0
Disulfides
0
Calcium
SY7Q814VUP
CASR protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
501Subventions
Organisme : Fondation pour la Recherche Médicale (Foundation for Medical Research in France)
ID : EQU202303016470
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 31070737
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 31371423
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 32330049
Informations de copyright
© 2024. The Author(s).
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