Adhesion G-protein coupled receptors: Implications for metabolic function

Abstract

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Opportunities and challenges for drug discovery in modulating Adhesion G protein-coupled receptor (GPCR) functions

“…Such a wide range of biological functions expectedly makes the aGPCR family a very tempting target for therapeutics; a notion increasingly supported by studies showing aGPCR involvement in human diseases [59,60,62,65,69,73]. The structural features also support aGPCR druggability, with several strategies to modulate the receptors' activity reported in the literature [6].…”

“…Additionally, ADGRC1, along with ADGRG6 and ADGRV1 were identified to be expressed in the vestibular, auditory, and visual systems, and have been implicated in their functionality and development [68]. The subfamily C (ADGRC2 and 3), together with ADGRG1 and ADGRF5 are implicated in the proper functioning of the endocrine system, particularly pancreas [69]; ADGRC2 is also linked to the lipids metabolism [70]. ADGRL1, ADGRL4, and ADGRG1 are reported to be strongly expressed in the pancreatic islet cells [69].…”

“…The subfamily C (ADGRC2 and 3), together with ADGRG1 and ADGRF5 are implicated in the proper functioning of the endocrine system, particularly pancreas [69]; ADGRC2 is also linked to the lipids metabolism [70]. ADGRL1, ADGRL4, and ADGRG1 are reported to be strongly expressed in the pancreatic islet cells [69]. In the gastrointestinal (GI) system, ADGRE5 is reported to be noticeably expressed in the human intestinal epithelium [71].…”

“…In the gastrointestinal (GI) system, ADGRE5 is reported to be noticeably expressed in the human intestinal epithelium [71]. Several other receptors are reported to exhibit noticeable presence in the GI tissue as well, including the G subfamily ADGRG7, ADGRG1, ADGRG2, and ADGRG6 [69]. Important to mention, other vertebrate species, such as rodents (mice, rats) or zebrafish, which are commonly employed in drug discovery studies, are characterized by several important differences in the aGPCR repertoire.…”

Activation of GPR116/ADGRF5 by its tethered agonist requires key amino acids in extracellular loop 2 of the transmembrane region

“…Adhesion G Protein-Coupled Receptors (aGPCRs) are involved in a variety of pathophysiological processes, from development of the brain and the musculoskeletal system to modulation of metabolism (Olaniru et al, 2019), immune responsiveness and angiogenesis.…”