ADGRG1, an adhesion G protein-coupled receptor, forms oligomers

CEVHEROĞLU O., Demirbaş B., Öğütcü D., Murat M.

FEBS Journal, vol.291, no.11, pp.2461-2478, 2024 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 291 Issue: 11
  • Publication Date: 2024
  • Doi Number: 10.1111/febs.17117
  • Journal Name: FEBS Journal
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Food Science & Technology Abstracts, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.2461-2478
  • Keywords: ADGRG1/GPR56, BRET, FRET, G protein-coupled receptor, oligomerization
  • Ankara University Affiliated: Yes

Abstract

G protein-coupled receptor (GPCR) oligomerization is a highly debated topic in the field. While initially believed to function as monomers, current literature increasingly suggests that these cell surface receptors, spanning almost all GPCR families, function as homo- or hetero-oligomers. Yet, the functional consequences of these oligomeric complexes remain largely unknown. Adhesion GPCRs (aGPCRs) present an intriguing family of receptors characterized by their large and multi-domain N-terminal fragments (NTFs), intricate activation mechanisms, and the prevalence of numerous splice variants in almost all family members. In the present study, bioluminescence energy transfer (BRET) and Förster resonance energy transfer (FRET) were used to study the homo-oligomerization of adhesion G protein-coupled receptor G1 (ADGRG1; also known as GPR56) and to assess the involvement of NTFs in these receptor complexes. Based on the results presented herein, we propose that ADGRG1 forms 7-transmembrane-driven homo-oligomers on the plasma membrane. Additionally, Stachel motif interactions appear to influence the conformation of these receptor complexes.