The Role of Claudins in Determining Paracellular Charge Selectivity

Abstract

Tight junctions create regulated barriers in the paracellular space between epithelial cells, including those of the airway and alveolus. Junctions vary widely throughout the body in their electrical resistance and, to some extent, in their ionic charge selectivity. Paracellular differences complement transcellular transport to define overall water, ion, and solute movements. A large family of transmembrane proteins called claudins has recently been implicated in creating the variable properties of the junction. Here we highlight the evidence that claudins are functional components of the barrier. Supportive data include evidence from deletion of selected claudins in mice, human genetic diseases of claudins 14 and 16, and direct experimental tests of the hypothesis that the extracellular charged residues on claudins influence the passage of ions through the junction. Alterations in claudin expression profiles may contribute to epithelial lung dysfunction during infection and inflammation. Much work remains to be done in the molecular characterization of tight junctions in the lung in normal physiology and during pathologic processes.

Prolactin-stimulated transepithelial calcium transport in duodenum and Caco-2 monolayer are mediated by the phosphoinositide 3-kinase pathway

“…The charge-selective property of the tight junction could be demonstrated by P Na , P Cl , and their ratio (27,31,57). Normally, the paracellular channels in the small intestine intrinsically favored positively charged molecules and ions, i.e., high P Na /P Cl ratio (24,57), as confirmed by P Na /P Cl of 2.4 and 3.7 in the duodenum and Caco-2 monolayer, respectively.…”

“…Since PRL stimulated the paracellular calcium transport in both duodenal epithelium and Caco-2 monolayer, we determined the epithelial charge selectivity, which was known to influence transport of several ions through the paracellular pathway (19,57). In the duodenum, 800 ng/ml PRL increased P Na /P Cl from a control value of 2.40 Ϯ 0.06 (n ϭ 8) to 3.16 Ϯ 0.23 (n ϭ 8, P Ͻ 0.01; Fig.…”

Molecular Determinants of Magnesium Homeostasis

“…45,46 Their localization and both intracellular and intercellular interactions are postulated to form pores that regulate paracellular movement of ions. 47,48 Absent or faulty claudin-16 activity could therefore prevent the reabsorption of Mg 2ϩ (as well as Ca 2ϩ ) and result in FHHNC. Consistent with this hypothesis is the recent observation that a similar phenotype is observed in individuals with mutations in claudin-19, which is also located at the tight junction of the TAL.…”

Claudin-1, −2, −3, −4, −5, and −7 in Usual Interstitial Pneumonia and Sarcoidosis

“…Both types of junctions have been shown to exist in alveolar epithelium of lung, but there is no detailed knowledge of their function, and even their distribution in normal and diseased human lung is poorly understood. The tight junctions vary in the different epithelia, and they are often divided into leaky and tight types (Van Itallie and Anderson 2004). Less than a decade ago, it was observed that claudins are the main family of proteins that make up the tight junctions (Tsukita et al 2001).…”