Functional analysis of the adhesion GPCR class in Drosophila

• Applicants: Professor Dr. Tobias Langenhan; Dr. Nicole Scholz
• Subject Area: Anatomy and Physiology ; Pharmacology
• Term: from 2014 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 246212759

Adhesion-GPCRs (aGPCRs) possess a highly modular blueprint thatenables canonical G-protein and beta-arrestin signaling through aheptahelical transmembrane unit (7TM) as well as adhesion andtarget recognition mediated by large extracellular domains. In contrastto other GPCR families, aGPCRs engage primarily with insolubleligands presented by adjacent cells or the extracellular matrix. Theligand nature and the conspicuous receptor geometry may reflect thecapacity of aGPCRs to sense mechanical cues, an unusual sensorymodality within the GPCR realm. Several studies have demonstratedaGPCR function in mechanobiological phenomena, however severalprincipal mechanistic aspects of how these receptors operate, whichsignaling cascades they trigger in response to mechanical stimulationand finally how these signals are implemented into the cellularprogram to modulate its physiology are unknown. Furthermore, recentwork on Latrophilin/dCirl indicates that the dimension of the ECDshapes its mechanoceptive profile and that alternative splicing ofLatrophilin/dCirl mRNA yields receptor isoforms that vary greatly inECD size. This project utilizes Drosophila as an in vivo test tube toinvestigate the biological relevance of natively occuring dCIRLreceptor isoforms with a particular focus on their mechanosensingand signaling capabilities. We will also explore the possibility thataGPCRs employ alternative signaling routes to shape cellularbehavior. The second part of this project focuses on the functionalcharacterization of two newly identified, unsought aGPCRs (CG11318and CG15556). Finally, we will explore if they operate inmechanobiological contexts in vivo and if so how these inputs areintegrated to modify the biology of the expressing tissues.

• DFG Programme: Research Units
• Subproject of: FOR 2149: Elucidation of Adhesion-GPCR Signalling