Claudin clusters as determinants of epithelial barrier function

Claudins are tetraspan tight junction proteins which have been attributed to primarily determine epithelial barrier function in a wide variety of different organs and tissues. Among this protein family with currently 27 members, single claudins contribute in an organ‐ and tissue‐specific manner to defined properties such as cation‐, anion‐ or water‐selective pore functions, sealing functions or ambiguous functions. As the size of tight junction strand particles visualized by freeze‐fracture electron microscopy have a diameter of approximately 10 nm, multimeric assembly of tight junction proteins appears to be a basic principle for barrier formation. Moreover, expression patterns of different tissues showed that single claudins appear to specifically co‐localize with other claudins, which indicates a cluster formation within tight junction strand particles with a fixed stoichiometry. This review provides a critical view on the current understanding of tight junction protein co‐localization within strands. We analyze how tissue specific differences of claudin functions could be dependent on their specific partners for barrier formation. Furthermore, a model of claudin clusters as structural and functional units within tight junction strands is provided. © 2015 IUBMB Life, 67(1):29–35, 2015