Prof. Dr. Robert Tampé
Goethe University, Institute of Biochemistry, Cellular Biochemistry
Transmembrane signaling by dynamic in-situ receptor confinement
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.
Project related references:
- Sánchez MF, Els-Heindl S, Beck-Sickinger AG, Wieneke R, Tampé R (2021) Photo-induced receptor confinement drives ligand-independent GPCR signaling. Science 371, abb7657, in press.
- Gatterdam K, Joest EF, Dietz MS, Heilemann M, Tampé R (2018) Super-chelators for advanced protein labeling in living cells. Angew Chem Int Ed 57, 5620-5.
- Kollmannsperger A, Sharei A, Raulf A, Heilemann M, Langer R, Jensen KF, Wieneke R, Tampé R (2016) Live-cell protein labelling with nanometre precision by cell squeezing.
Nature Communications 7, 10372.