Paracellin-1, a Renal Tight Junction Protein Required for Paracellular Mg ²⁺ Resorption

TLDR

Tight junctions regulate paracellular transport, yet the specific proteins mediating renal magnesium reabsorption in the thick ascending limb remain poorly defined. Positional cloning revealed that mutations in the tight‑junction protein paracellin‑1 cause renal magnesium wasting, establishing it as a key component of selective paracellular Mg²⁺ reabsorption.

Abstract

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 (Mg 2+ ) 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 in which cause renal Mg 2+ wasting. PCLN-1 is located in tight junctions of the TAL and is related to the claudin family of tight junction proteins. These findings provide insight into Mg 2+ homeostasis, demonstrate the role of a tight junction protein in human disease, and identify an essential component of a selective paracellular conductance.