Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na + and Mg 2+ transport

Significance The thick ascending limb (TAL) of Henle’s loop is a nephron segment that reabsorbs Na+ , Ca2+ , and Mg2+ via the paracellular pathway, the tight junction (TJ). TJ permeability is regulated by claudin proteins. We show that the TAL expresses claudins cldn3, cldn10b, cldn16, and cldn19 in a TJ mosaic pattern with cldn3/cldn16/cldn19 in a complex and cldn10b alone. This mutual exclusiveness is facilitated by different claudin interaction properties. TJs with cldn10b favor Na+ over Mg2+ , whereas TJs with cldn3/cldn16/cldn19 prefer Mg2+ over Na+ . Hence we conclude that mono- and divalent cations in the TAL take different paracellular routes, and their reabsorption can be regulated independently. This spatial separation is important for renal ion homeostasis and its discovery improves our understanding of paracellular transport organization.