Project Details
Projekt
Phase separation of membrane scaffolding proteins as a mechanism to control formation of tight junctions
Subject Area
Cell Biology
Biochemistry
Biophysics
Biochemistry
Biophysics
Term
since 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 419138182
Tight junctions control tissue integrity and para-cellular flux of solutes in epithelial and endothelial tissues. The junction is a supra-molecular complexes comprised of adhesion receptors, scaffolding and adapter proteins and cytoskeletal components which are located in a highly dynamic membrane attached plaque. Nucleation and organization of tight junctions requires a mechanism to accumulate the necessary junctional components and facilitate polymerization of claudin receptors and actin filaments at the membrane. In the first funding period we have established that the main scaffolding proteins (ZO) of the tight junction form membrane attached compartments via surface phase separation (prewetting) and that phase separation of ZO proteins is required for junction formation. In the next period, we propose to study how ZO phase separation contributes to structure formation of the tight junction network and its positioning at the apical interface. We propose to address this questions via our established interdisciplinary combination of cell biology and in vitro biochemistry/biophysics (Honigmann) with non-equilibrium thermodynamic theory (Weber). We believe that this work will provide new mechanisms how the tight junction is formed and positioned. Additionally, this project will generate important general concepts about the function of protein phase separation for controlling biochemical reactions and inducing the formation of structured supra-molecular assemblies.
DFG Programme
Priority Programmes
