Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption

Epithelia permit selective and regulated flux from apical to basolateral surfaces by transcellular passage through cells or paracellular flux between cells. Tight junctions constitute the barrier to paracellular conductance; however, little is known about the specific molecules that mediate paracellular permeabilities. Renal magnesium ion (Mg²⁺) resorption occurs predominantly through a paracellular conductance in the thick ascending limb of Henle (TAL). Here, positional cloning has identified a human gene, paracellin-1 (PCLN-1), mutations on which cause renal Mg²⁺ wasting. PCLN-1 is located in tight junctions of the TAL and is related to the claudin family of tight junction proteins. These finding provide insight into Mg²⁺ homeostasis, demonstrate the role of a tight junction protein in human disease, and identify an essential component of selective paracellular conductance.