Proteolytic processing of adhesion G-protein coupled receptors through proteases

• Applicant: Professor Dr. Tobias Langenhan
• Subject Area: Pharmacology ; Biochemistry ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 542631574

Adhesion-type G protein-coupled receptors (aGPCRs) constitute a family of more than 30 mammalian (32 human) surface sensors with pivotal roles in developmental processes of all tissues and organs. Due to their control of migration, proliferation, lineage specification, and morphologies of cell types, the genetic damage of their encoding loci through germline and somatic mutations have been emerging as driving events in the pathogenesis of multiple ailments including diseases of the nervous, immune and cardiovascular systems, and in cancerogenesis and metastasis. While current research primarily investigates the activation of aGPCRs by adhesive ligand interactions and mechanical cues, their extracellular region can also be subject to proteolytic processing, which may impact their signaling. However, no systematic analysis of aGPCR-protease interactions across the entire aGPCR family and throughout the scope of known proteases with extracellular activity has been conducted to date. This project pursues the identification of proteases that target extracellular components of aGPCRs in vivo using the fruitfly Drosophila melanogaster, the characterization of the proteolytic process of aGPCR-cleavage by ADAM17 or ADAM10 proteases, and the evaluation of ADAM10/17-dependence of aGPCR activity.

• DFG Programme: Research Grants
• International Connection: Poland
• Partner Organisation: Narodowe Centrum Nauki (NCN)
• Cooperation Partner: Dr. Renata Mezyk-Kopec