Selective Interactions of Mouse Melanocortin Receptor Accessory Proteins with Somatostatin Receptors.
G protein-coupled receptors
heterodimerization
melanocortin receptor accessory protein 1
somatostatin receptor
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
13 01 2022
13 01 2022
Historique:
received:
11
11
2021
revised:
28
12
2021
accepted:
06
01
2022
entrez:
21
1
2022
pubmed:
22
1
2022
medline:
24
2
2022
Statut:
epublish
Résumé
Somatostatin receptors (SSTRs) are G protein-coupled receptors (GPCRs) known to regulate exocrine secretion, neurotransmission, and inhibit endogenous cell proliferation. SSTR subtypes (SSTR1-SSTR5) exhibit homo- or heterodimerization with unique signaling characteristics. Melanocortin receptor accessory protein 1 (MRAP1) functions as an allosteric modulator of melanocortin receptors and some other GPCRs. In this study, we investigated the differential interaction of MRAP1 and SSTRs and examined the pharmacological modulation of MRAP1 on mouse SSTR2/SSTR3 and SSTR2/SSTR5 heterodimerization in vitro. Our results show that the mouse SSTR2 forms heterodimers with SSTR3 and SSTR5 and that MRAP1 selectively interacts with SSTR3 and SSTR5 but not SSTR2. The interactive binding sites of SSTR2/SSTR3 or SSTR2/SSTR5 with MRAP1 locate on SSTR3 and SSTR5 but not SSTR2. The binding sites of MRAP1 to SSTR3 are extensive, while the ones of SSTR5 are restricted on transmembrane region six and seven. The heterodimerization of mouse SSTR2, SSTR3, and SSTR5 can be modulated by binding protein in addition to an agonist. Upregulation of extracellular signal-regulated kinases phosphorylation, p27
Identifiants
pubmed: 35053382
pii: cells11020267
doi: 10.3390/cells11020267
pmc: PMC8773839
pii:
doi:
Substances chimiques
MRAP protein, mouse
0
Membrane Proteins
0
Receptors, Somatostatin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Key Research and Development Program of China
ID : 2017YFA0103902 & 2019YFA0111400
Organisme : The National Natural Science Foundation of China
ID : 31771283
Organisme : Innovative Research Team of High-level Local Universities in Shanghai
ID : SSMU-ZDCX20180700
Organisme : the Key Laboratory Program of the Education Commission of Shanghai Municipality
ID : ZDSYS14005
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