Physiological relevance and signaling mechanisms of the Adhesion GPCR GPR110
Simone Prömel, Leipzig University
Adhesion G protein-coupled receptors (aGPCRs) fulfil essential functions in developmental, immunological and neurological processes and have been shown to be highly relevant in various pathological settings. Their exceptional architecture indicates unique signaling mechanisms for this receptor class. One group of aGPCRs which is highly suitable for studies on activation and signaling due to the conservation and common ancestry of its members is the cluster of Gpr110/Adgrf1, Gpr111/Adgrf2, Gpr115/Adgrf4 and Gpr116/Adgrf5. It has been shown that among receptors of this cluster, each aGPCR mediates distinct signals, but a tethered agonist derived from one receptor is able to activate several members of this group. Several studies suggest that these receptors are associated with vital biological processes with GPR110 as one of the oldest members being predominantly linked to metabolic functions. Despite these indications and their interesting signaling capacities, their physiological functions remain vastly elusive precluding the evaluation of the impact of their signals. A mouse model knockout for Gpr110 revealed that this receptor potentially plays a role in regulation of metabolic processes and renal function.
Röthe J, Thor D, Winkler J, Knierim A, Binder C, Huth S, Kraft R, Rothemund S, Schöneberg T, Prömel S (2019) Involvement of the Adhesion GPCRs Latrophilins in the Regulation of Insulin Release. Cell Reports. 26: 1573–1584.
Matúš D, Prömel S (2018) G Proteins and GPCRs in C. elegans Development: A Story of Mutual Infidelity. Journal of Developmental Biology. 2018; 6. pii: E28. doi: 10.3390/jdb6040028.