FOR 2149:  Elucidation of Adhesion-GPCR Signalling

• Subject Area: Medicine
• Term: from 2014 to 2024
• Website: Homepage
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246212759

Adhesion-type G protein-coupled receptors form a large class ofseven-transmembrane spanning (7TM) receptors. 7TM receptorshave proven the linchpin for countless physiological functions and atreasure trove for modern pharmaceutical intervention. Adhesion-GPCR appear in stark contrast to the rest of the 7TM receptorsuperfamily as they are by far the most poorly understood 7TMreceptor class. The scientific aims of the Research Unit focus onseveral fundamental aspects of adhesion GPCR biology pertaining tothe physiological and pharmacological features of their signaling.These include their role of mechanosensors, the presence of tetheredagonism as the signal transducing step upon their activation, theanalysis of non-canonical signals controlled through adhesion GPCRsand their effect on cytoskeletal dynamics. In addition, the ResearchUnit strives to deconstruct the impact of adhesion GPCRs on theemergence of neoplasias and inflammation. These questions aretargeted from different methodological angles encompassingphysiology, biochemistry, structural and cell biology, pharmacology,optogenetics and nanoscopic imaging techniques. Importantly, thestrengths of invertebrate and vertebrate models will be used tosynergise efforts in linking molecular steps in adhesion-GPCRsignalling to physiological processes governed by these unusualreceptors. Specific care is dedicated to interlock the projects not onlymethodologically, but especially at the conceptual level to facilitate theextraction of general principles of adhesion-GPCR signalling.

• DFG Programme: Research Units
• International Connection: Netherlands

Projects

• Adhesion GPCR signaling in hematopoietic stem and progenitor cells (Applicant Pabst, Caroline )
• Adhesion GPCRs in inflammatory diseases of the human brain (Applicant Hamann, Jörg )
• Coordination Funds (Applicant Langenhan, Tobias )
• Delineating the role of CTF and NTF of Gpr126 in physiology and pathophysiology (Applicant Engel, Felix B. )
• Evaluation of CD97 signaling in transgenic mice (Applicant Aust, Gabriela )
• Functional analysis of the adhesion GPCR class in Drosophila (Applicants Langenhan, Tobias ;  Scholz, Nicole )
• Interaction of adhesion GPCR signalling and ionotropic pathways during mechano-sensory signal transduction (Applicants Kittel, Robert J. ;  Langenhan, Tobias )
• Physiological relevance and signaling mechanisms of the Adhesion GPCR GPR110 (Applicant Prömel, Simone )
• Structural studies on extracellular adhesion GPCR signaling (Applicants Schöneberg, Torsten ;  Sträter, Norbert )
• The role of the Adhesion G protein-coupled receptor GPR133/ADGRD1 in the mechano-sensitive tissues heart and bone (Applicant Liebscher, Ines )
• VLGR1 signaling at focal adhesions and ICD release as a non-canonical signaling pathway of aGPCRs (Applicant Wolfrum, Uwe )

• Spokesperson: Professor Dr. Tobias Langenhan