loading page

Downstream signaling of disease-associated mutations on GPR56/ADGRG1
  • +2
  • Orkun Cevheroglu,
  • Nil Demir,
  • Seçkin Kesici,
  • Salih Özçubukçu,
  • Çağdaş Son
Orkun Cevheroglu
Ankara University

Corresponding Author:[email protected]

Author Profile
Nil Demir
Middle East Technical University
Author Profile
Seçkin Kesici
Middle East Technical University
Author Profile
Salih Özçubukçu
Middle East Technical University
Author Profile
Çağdaş Son
Middle East Technical University
Author Profile


GPR56/ADGRG1 is an adhesion GPCR and mutations on this receptor cause cortical malformation due to the over-migration of neural progenitor cells on the brain surface. At the pial surface, GPR56 interacts with collagen III, induces Rho dependent activation through Gα12/13 and inhibits the neuronal migration. In human glioma cells, GPR56 inhibits cell migration through Gαq/11 dependent Rho pathway. GPR56-tetraspanin complex is known to couple with Gαq/11. GPR56 is an aGPCR that couples with various G proteins and signals through different downstream pathways. In this study, BFPP mutants disrupting GPR56 function but remain to be expressed on plasma membrane were used to study receptor signaling through Gα12, Gα13 and Gα11 with BRET biosensors. GPR56 showed coupling with all three G proteins and activated heterotrimeric G protein signaling upon stimulation with Stachel peptide. However, BFPP mutants showed different signaling defects for each G protein indicative of distinct activation and signaling properties of GPR56 for Gα12, Gα13 or Gα11. β-arrestin recruitment was also investigated following the activation of GPR56 with Stachel peptide using BRET biosensors. N-terminally truncated GPR56 showed enhanced β-arrestin recruitment, however neither wild-type receptor nor BFPP mutants gave any measurable recruitment upon Stachel stimulation, pointing different activation mechanisms for β-arrestin involvement.
09 Jan 2023Submitted to Basic & Clinical Pharmacology & Toxicology
10 Jan 2023Review(s) Completed, Editorial Evaluation Pending
10 Jan 2023Submission Checks Completed
10 Jan 2023Assigned to Editor
10 Jan 2023Reviewer(s) Assigned
07 Feb 2023Editorial Decision: Revise Minor
02 Mar 20231st Revision Received
03 Mar 2023Submission Checks Completed
03 Mar 2023Assigned to Editor
03 Mar 2023Review(s) Completed, Editorial Evaluation Pending
06 Mar 2023Reviewer(s) Assigned
01 Apr 2023Editorial Decision: Accept