Project 05

The role of the Adhesion G protein-coupled receptor GPR133/ADGRD1 in the mechano-sensitive tissues heart and bone

Ines Liebscher, Leipzig University 

Team members
Caroline Wilde

Project Description
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.

Publications

Bradley EC, Cunningham RL, Wilde C, Morgan RK, Klug EA, Letcher SM, Schöneberg T, Monk KR, Liebscher I, Petersen SC (2019) In vivo identification of small molecules mediating Gpr126/Adgrg6 signaling during Schwann cell development. Annals of the New York Academy of Sciences doi: 10.1111/nyas.14233. [Epub ahead of print]. 

Eichler W, Lohrenz A, Simon KU, Krohn S, Lange J, Bürger S, Liebscher I (2019) The role of ADGRE5/CD97 in human retinal pigment epithelial cell growth and survival. Annals of the New York Academy of Sciences. doi: 10.1111/nyas.14210. [Epub ahead of print]. 

Morgan RK, Anderson GR, Araç D, Aust G, Balenga N, Boucard A, Bridges JP, Engel FB, Formstone CJ, Glitsch MD, Gray RS, Hall RA, Hsiao CC, Kim HY, Knierim AB, Kusuluri DK, Leon K, Liebscher I, Piao X, Prömel SScholz N, Srivastava S,Thor D, Tolias KF, Ushkaryov YA, Vallon M, Van Meir EG, Vanhollebeke B, Wolfrum U, Wright KM, Monk KR, Mogha A (2019). The expanding functional roles and signaling mechanisms of adhesion G protein-coupled receptors. Annals of the New York Academy of Sciences. doi: 10.1111/nyas.14094. [Epub ahead of print] 

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 IHamann 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. 

Knierim AB, Röthe J, Çakir MV, Lede V, Wilde C, Liebscher I, Thor D, Schöneberg T. Genetic basis of functional variability in adhesion G protein-coupled receptors. Sci Rep. 2019; 9:11036.