Transmembrane signaling by in-situ receptor confinement

• Applicant: Professor Dr. Robert Tampé
• Subject Area: Biochemistry ; Biological and Biomimetic Chemistry ; Biophysics
• Term: from 2021 to 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 468346185

Cell-cell communication is crucial for multicellular organisms and relies on the dynamic assembly of receptor-ligand complexes at the plasma membrane. Receptor clustering is a key process in signal transduction and pleiotropic downstream cell responses. Heterotrimeric G protein-coupled receptors (GPCRs) are members of a large family of membrane proteins, which mediate a myriad of cellular processes. The physiological relevance of receptor clustering or confinement is, however, poorly understood. In this proposal, we aim to control the membrane organization of GPCRs in-situ and reveal how location, lateral diffusion, density, and confinement of receptors modulate early signaling events and the final physiological outcome. Our integrative approach, using small synthetic photo-activatable lock-and-key pairs, photo-instructive matrices, and G protein sensors, brings us in the unique position to study receptor clustering in living cells. We aim at a cutting-edge combination of (opto)chemical biology, membrane biochemistry, cellular biophysics, and imaging techniques to decode the mechanism underlying GPCR activation by confinement and downstream signaling by confinement.

• DFG Programme: Research Grants