Claudin-16 and claudin-19 function in the thick ascending limb.
OBJECTIVE
Claudin-16 and claudin-19 play a major role in the regulation of magnesium reabsorption in the thick ascending limb (TAL). This review describes recent findings of the physiological function of claudin-16 and claudin-19 underlying normal transport function for magnesium reabsorption in the TAL.


RESULTS
Mutations in the genes encoding the tight junction proteins claudin-16 and claudin-19 cause the inherited human renal disorder familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The cation selectivity of the tight junction is vital for generating the lumen positive transepithelial potential in the TAL, which drives paracellular absorption of magnesium. Claudin-16 and claudin-19 require each other for assembly into tight junctions in the TAL. Heteromeric claudin-16 and claudin-19 interaction forms a cation selective tight junction paracellular channel. Loss of either claudin-16 or claudin-19 in the mouse kidney abolishes the cation selectivity for the TAL paracellular pathway, leading to excessive renal wasting of magnesium.


CONCLUSIONS
Epithelial paracellular channels are increasingly understood to be formed from claudin oligomeric complexes. In the mouse TAL, claudin-16 and claudin-19 cooperate to form cation-selective paracellular channels required for normal levels of magnesium reabsorption. Different subsets of the claudin family of tight junction proteins are found distributed throughout the nephron, and understanding their roles in paracellular ion transport will be fundamental to understanding renal ion homeostasis.
Hou
Jianghui
J
Washington University School of Medicine, Division of Renal Diseases, St Louis, Missouri, USA.
Goodenough
Daniel A
DA
D000042:Absorption; D000818:Animals; D057167:Claudins; D006801:Humans; D053565:Hypercalciuria / Q000378:metabolism; D017136:Ion Transport; D008138:Loop of Henle / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D009397:Nephrocalcinosis / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism
C508912:CLDN19 protein, human; D057167:Claudins; D008565:Membrane Proteins; C502010:claudin 16; D012964:Sodium; D008274:Magnesium