The role of the Adhesion G protein-coupled receptor GPR133/ADGRD1 in the mechano-sensitive tissues heart and bone
Ines Liebscher, Leipzig University
Identifying the activation mechanism of adhesion G protein-coupled receptors (aGPCRs) has been the main goal of this project. We were able to define a tethered agonist region, establish derived agonistic and antagonistic peptides and showed one possible way to achieve aGPCR activation in vivo and in vitro through an orchestrated sequence including binding of an extracellular interaction partner, mechanical force and tethered agonist-mediated activation of intracellular signaling cascades. We now aim to translate these findings into the characterization of the consequences of the deletion of an orphan aGPCR, the GPR133/ADGRD1 in zebrafish and mice in tissues that are known to respond to or work through mechanical forces, bone and heart.
Hilbig D, Sittig D, Hoffmann F, Rothemund S, Warmt E, Quaas M, Stürmer J, Seiler L, Liebscher I, Hoang NA, Käs JA, Banks L, Aust G (2018) Mechano-Dependent Phosphorylation of the PDZ-Binding Motif of CD97/ADGRE5 Modulates Cellular Detachment. Cell Rep. 24: 1986-1995.
Hsiao CC, Chu TY, Wu CJ, van den Biggelaar M, Pabst C, Hébert J, Kuijpers TW, Scicluna BP, I KY, Chen TC, Liebscher I, Hamann J, Lin HH (2018) The Adhesion G Protein-Coupled Receptor GPR97/ADGRG3 Is Expressed in Human Granulocytes and Triggers Antimicrobial Effector Functions. Frontiers in Immunology. 9:2830. fimmu.2018.02830. eCollection.