Signal integration and specification of adhesion GPCRs (B05)

• Subject Area: Biochemistry ; Pharmacology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 421152132

Project B05 wants to investigate, which specific intracellular signaling pathways of an adhesion GPCR are activated by different stimuli. Based on the observation that N-terminal ligands of the adhesion GPCR GPR126/ADGRG6 can induce a Gs/Gi-preference in signal transduction we aim to decipher the complex intra-cellular cascades that result from this G protein bias including the engagement of so far unknown non-canonical signals mediated by different kinases and arrestins. We will study the signaling preferences of a whole subset of activators that we established in the first funding period. To tackle this endeavour, we will employ a combination of classic biochemical methods such as co-immunoprecipitation and Western blotting as well as conformational biosensors and reporter assays. We further aim to identify the structural basis of signaling bias on GPR126/ADGRG6 for which we will tightly collaborate with experts in structural biology and computational modelling within the CRC.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1423: Structural Dynamics of GPCR Activation and Signaling
• Applicant Institution: Universität Leipzig
• Project Head: Professorin Dr. Ines Liebscher