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

Epithelia permit selective and regulated flux from apical to basolateral su rfaces 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 paracell ular permeabilities. Renal magnesium ion (Mg2+) resorption occurs predomina ntly through a paracellular conductance in the thick ascending limb of Henl e (TAL), Here, positional cloning has identified a human gene, paracellin-1 (PCLN-1), mutations in which cause renal Mg2+ wasting. PCLN-1 is Located i n tight junctions of the TAL and is related to the claudin family of tight junction proteins. These findings provide insight into Mg2+ homeostasis, de monstrate the role of a tight junction protein in human disease, and identi fy an essential component of a selective paracellular conductance.