Molecular and structural pattern of claudin-claudin interactions in tight junctions

Figure from
Nastech Pharmaceutical Company Inc.

Figure from C.M. Van Itallie, J.M. Anderson
Physiology 19, 331-338 (2004)

Tight junctions are barriers between epithelial and endothelial cells but they also form pores and channels of different selectivity in-between cells. They are characterized by a tissue, organ or cell specific combination of proteins of the claudin, occluding, tricellulin and JAM families. Beside those transmembrane proteins that determine the varying properties of barriers and pores, a number of cytoplasmatic associated adaptor proteins are present, that mediate the regulation and connection of the tight junctions with the actic cytoskeleton. Signal transduction is taking place both ways: tight junctions are regulated intracellularly and they in turn influence gene expression, proliferation and cell differentiation.

The interaction in between the different claudin subtypes and the varying function (pore or seal) depending on the different claudin combination is not yet understood. In this project we want to study the paracellular interactions of claudin subtypes using molecular biology, bioinformatics and NMR spectroscopy in order to identify the molecular and structural patterns that determine the functionality of a given claudin combination. Experiments will be performed to test a starting hypothesis for the interaction between the extracellular loop 1.

last changes 09.03.2013, Peter Schmieder