Role of intercellular junction formation and maintenance in epithelial barrier formation and renewal.

Epithelia form physical and functional barriers that are exposed to a wide range of mechanical stresses. With focal adhesions (FAs) cell–matrix adhesions are present in the basal region to connect the extracellular basement membrane with the actin cytoskeleton. Cadherin based adherens junctions (AJs) and desmosomes connect intercellular adhesion through different cytoplasmic linker proteins to actin and intermediate filament systems respectively, thus allowing neighboring cells to act as mechanical units to withstand and respond to these stresses. How junctions coordinate their formation and how their molecular composition and dynamics change when exposed to mechanical stress is largely unknown. Moreover, how mechanically damaged junctional proteins are removed is not known.

The overall aim of my project is to understand how intercellular junctions are formed and dynamically maintained to enable epithelial barrier formation and renewal. One part of the project focus on understanding how the mechanosensitive interactions of the cadherin-catenin complex control desmosome formation, the other part of the project aim at how junctions maintain healthy proteostasis in the face of mechanical stress to promote mechanical resistance.

Hanyin Zhang, Ph.D Student.