Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium

摘要: Claudins are tight junction integral membrane proteins that key regulators of the paracellular pathway. Defects in claudin-16 (CLDN16) and CLDN19 function result inherited human renal disorder familial hypomagnesemia with hypercalciuria nephrocalcinosis (FHHNC). Previous studies showed siRNA knockdown CLDN16 mice results a mouse model for FHHNC. Here, we show CLDN19-siRNA also developed FHHNC symptoms chronic wasting magnesium calcium together defective salt handling. caused loss from junctions thick ascending limb (TAL) without decrease expression level, whereas produced similar effect on CLDN19. In both lines, CLDN10, CLDN18, occludin, ZO-1, normal constituents TAL junctions, remained correctly localized. CLDN16- CLDN19-depleted had barrier but ion selectivity. These data, yeast two-hybrid binding studies, indicate heteromeric interaction was required assembling them into structure generating cation-selective channels.