Fanning - Research

Role of Cytoplasmic Proteins in Tight Junction Assembly and Function

My research interests are primarily focused on the molecular basis of tight junction assembly and permeability. Tight junctions are the primary barrier to the paracellular transport of ions, macromolecules, and immune cells across an epithelium, and are thus critical to the maintenance of distinct tissue spaces. The protein Zonula Occludens (ZO)-1 is a cytosolic component of the tight junction, and my previous work has suggested that this protein has a key role organizing transmembrane proteins that seal the paracellular space. More recently, I have shown that ZO-1 binds directly to the actin cytoskeleton and have characterized the interaction of ZO-1 with several other actin-binding proteins, including the tyrosine kinase substrate cortactin and the adherens junction protein alpha catenin. These observations suggest that that ZO-1 provides an important functional connection between components of the paracellular seal and the actin cytoskeleton.