claudin

Claudins are a family of integral membrane proteins that are core components of tight junctions in epithelial and endothelial cells. They regulate the paracellular pathway, influencing the passage of ions and small solutes between adjacent cells and contributing to the barrier properties of tissues.

Each claudin molecule is a four-pass transmembrane protein with cytoplasmic N- and C- termini. Two extracellular loops form the interfaces between neighboring cells, helping to seal the paracellular space and determine ion selectivity. The C-terminal cytoplasmic tail often contains a PDZ-binding motif that associates with scaffolding proteins such as ZO-1, ZO-2, and ZO-3, linking claudins to the cytoskeleton and other tight junction components. Claudins can form both homo- and heterotypic interactions across cell borders, assembling into continuous tight junction strands.

Claudins comprise a large gene family, with multiple members expressed in different tissues. In humans there are numerous claudins (a multigene family with members expressed in epithelia and endothelia), and their tissue-specific expression patterns contribute to organ-specific barrier properties. The combination of claudin types in a given tight junction influences permeability to specific ions, charge, and solutes. Expression and function are dynamically regulated by signaling pathways, phosphorylation, endocytosis, and interactions with other tight junction proteins.

Dysregulation or mutation of claudins is associated with various diseases, including kidney, ear, and skin disorders, and altered claudin expression is observed in inflammatory and neoplastic conditions. Some pathogens and toxins target claudins to modulate barrier function. Claudins are also used in research and biotechnology to study tight junction biology and to engineer epithelial barriers.