Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously.

Soluble α-klotho anchors TRPV5 to the distal tubular cell membrane independent of FGFR1 by binding TRPV5 and galectin-1 simultaneously. Am J Physiol Renal Physiol. 2021 Feb 22;: Authors: Lee J, Ju KD, Kim HJ, Tsogbadrakh B, Ryu H, Kang EJ, Kang MJ, Yang J, Kang HK, Ahn C, Oh KH Abstract Hypercalciuria is one of early manifestations of diabetic nephropathy (DN). This is partially due to a decrease in the expression of renal transient receptor potential vanilloid type 5 (TRPV5), which is responsible for renal calcium reabsorption. Soluble klotho was previously determined to increase TRPV5 by cleaving sialic acid, causing TRPV5 to bind to membrane protein galectin-1. However, a recent study showed that soluble klotho binds to α2-3-sialyllactose - where sialic acid is located - on TRPV5, rather than cleave it. Here, we report that soluble klotho tethers TRPV5 on the membrane by binding both TRPV5 and galectin-1, thereby protecting membrane TRPV5 from diabetes-induced endocytosis. We injected recombinant soluble α-klotho protein (rKL) into db/db and db/m mice for 8 weeks and collected urine and the kidney. We administered rKL, AZD4547 (FGFR1 inhibitor), and OTX008 (Galectin 1 inhibitor) to cultured mouse distal tubular cells, with or without 30 mM high glucose (HG) exposure. db/db mice showed increased renal calcium excretion and decreased renal TRPV5 expression. rKL treatment reversed this change. In vitro, TRPV5 expression in distal ...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research