claudins

Claudins are a family of integral membrane proteins that are major components of tight junctions in epithelial and endothelial tissues. They form the backbone of tight junction strands, regulating paracellular diffusion and contributing to transepithelial electrical resistance. The two extracellular loops of claudins participate in intercellular adhesion and largely determine the charge- and size-selective properties of the paracellular pathway.

Structurally, claudins are four-pass transmembrane proteins with cytoplasmic N- and C- termini. The C-terminus often contains a PDZ-binding motif that links claudins to scaffolding proteins such as ZO-1, ZO-2, and ZO-3, anchoring tight junctions to the actin cytoskeleton and coordinating junctional assembly and maintenance.

Diversity and tissue distribution: Humans express at least 24 claudins (CLDN1–CLDN24), with distinct tissue-specific expression patterns. The specific combination of claudins in a given tight junction determines its permeability characteristics, influencing selective passage of ions, water, and small solutes.

Regulation and dynamics: Claudin assembly and turnover are dynamic and subject to regulation by phosphorylation, endocytosis, and transcriptional control in response to developmental cues and environmental signals. These regulatory processes modulate barrier properties as tissues mature or respond to stress.

Clinical relevance: Altered claudin expression or pathogenic mutations can disrupt barrier function and contribute to disease. Examples include CLDN16 mutations causing hypomagnesemia with hypercalciuria and nephrocalcinosis, and mutations in other claudins associated with sensory or dermatological disorders. Aberrant claudin expression is also observed in various cancers and is explored as a diagnostic marker or therapeutic target.

Discovery and overview: Claudins were identified as tight junction proteins in epithelial cells, with foundational work in the late 1990s establishing their central role in barrier formation and function.