Phosphorylated claudin-16 interacts with Trpv5 and regulates transcellular calcium transport in the kidney

Significance Claudin is the core protein making the tight junction and the paracellular channel. Whether it may regulate the transcellular pathway is not known. Here, we have discovered that phosphorylated claudin-16 proteins are not localized in the tight junction but found in the luminal membrane of the distal tubular cells, where they facilitate the transcellular Ca ++ permeation via Trpv5. This discovery not only resolves a longstanding mystery pertaining to the role of transcellular Ca ++ pathway in the FHHNC syndrome, but also reveals a class of functional binding partners for Trp channels.