Physiological relevance and signaling mechanisms of the Adhesion GPCR GPR110

• Applicant: Professorin Dr. Simone Prömel
• Subject Area: Pharmacology ; Anatomy and Physiology
• Term: from 2014 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246212759

Adhesion G protein-coupled receptors (aGPCRs) fulfil essentialfunctions in developmental, immunological and neurologicalprocesses and have been shown to be highly relevant in variouspathological settings. Their exceptional architecture indicates uniquesignaling mechanisms for this receptor class. One group of aGPCRswhich is highly suitable for studies on activation and signaling due tothe conservation and common ancestry of its members is the clusterof Gpr110/Adgrf1, Gpr111/Adgrf2, Gpr115/Adgrf4 and Gpr116/Adgrf5.It has been shown that among receptors of this cluster, each aGPCRmediates distinct signals, but a tethered agonist derived from onereceptor is able to activate several members of this group. Severalstudies suggest that these receptors are associated with vitalbiological processes with GPR110 as one of the oldest membersbeing predominantly linked to metabolic functions. Despite theseindications and their interesting signaling capacities, theirphysiological functions remain vastly elusive precluding the evaluationof the impact of their signals. A mouse model knockout for Gpr110revealed that this receptor potentially plays a role in regulation ofmetabolic processes and renal function. The proposed projectfocuses on elucidation of the physiological functions of GPR110 andthe implications of its signaling mechanisms and targets two aims: 1.Analysis of the role of GPR110 in renal function and regulation ofmetabolic processes and 2. delineation of the signaling mechanismsunderlying these physiological functions. Based on own preliminarydata, these aims will be achieved using a combination of in vivo, exvivo and in vitro analyses centering around the existing knockoutmouse model, tissue culture models and the acquired knowledgeabout signaling of the receptor. The physiological relevance ofGPR110 in the kidney and a potential role in renal injury will beelucidated as well as its impact on regulation of metabolic processes.Subsequently, receptor signalling on a molecular level in the identifiedcontexts will be analyzed. Receptor activation and interaction partnerswill also be a focus of the project. The proposed research project willsubstantially contribute to the understanding of the physiologicalrelevance of the aGPCR GPR110. Moreover, findings will give furtherprofound insights into the signal transduction of aGPCRs, potentiallyaiding the evaluation of the pharmacological potential of this receptorclass.

• DFG Programme: Research Units
• Subproject of: FOR 2149: Elucidation of Adhesion-GPCR Signalling