Figure 7.

Proposed model for regulation of sKlotho by the renal CaSR. The left panel shows a diagram of a nephron with the DCT boxed. The middle panel shows two images of the DCT basolateral membrane where the CaSR, ADAM10, and Klotho are all expressed. In the top image, the CaSR is inactive, as is ADAM10, and there is no Klotho cleavage. In the bottom panel, the CaSR is activated by either Ca or increased pH, it activates ADAM10, increasing its protease activity, and ADAM10 cleaves membrane-bound Klotho. In the right panel, sKlotho leaves the kidney by the renal vein.