Investigating the homo-dimerization of ADGRD1/GPR133 and ADGRG5/GPR114 via resonance energy transfer techniques

Date

2023-6-01

Author

Demirbaş, Berkay

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G protein-coupled receptors (GPCRs) are the largest plasma membrane protein family in mammals. Through extracellular ligand binding, they go through a conformational change and a signaling cascade begins. Extracellular ligands that act on GPCRs can be hormones, neurotransmitters, ions, light, and even mechanical forces. In living cells, GPCRs are known to form homo- and/or hetero- oligomeric complexes. These complexes have impacts on receptor maturation, trafficking, and signaling. Adhesion G protein-coupled receptors (aGPCRs) constitute the second largest sub-family of GPCRs in mammals and they are known to interact with the extracellular matrix proteins and various other ligands on the cell surface and modulate the tissue and organ development. Adhesion GPCRs are amongst the least studied cell surface receptors hence their oligomeric structures are not yet fully understood, unlike other GPCR families. In the current study, two members of the aGPCRs, ADGRD1/GPR133 and ADGRG5/GPR114 were tagged with fluorescent and bioluminescent proteins, and their homo-oligomerization was studied using BRET and FRET in live cells. ADGRD1 is known to be upregulated in glioblastoma and ADGRG5 has significant roles in the immune cells. Therefore, understanding the receptor oligomerization and its consequences is crucial for these intriguing receptors which have important physiological and pathological roles. Our findings, for the very first time, suggest that ADGRD1 and ADGRG5 form oligomeric complexes, and the methods reported in this study will open the path for investigating the physiology of this receptor oligomerization.

Subject Keywords

Adhesion GPCR, ADGRD1, ADGRG5, Dimerization, RET

URI

https://hdl.handle.net/11511/104341

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Graduate School of Natural and Applied Sciences, Thesis