| First Author | Abousaab A | Year | 2016 |
| Journal | Cell Physiol Biochem | Volume | 40 |
| Issue | 5 | Pages | 874-882 |
| PubMed ID | 27941311 | Mgi Jnum | J:324449 |
| Mgi Id | MGI:6783233 | Doi | 10.1159/000453146 |
| Citation | Abousaab A, et al. (2016) beta-Klotho as a Negative Regulator of the Peptide Transporters PEPT1 and PEPT2. Cell Physiol Biochem 40(5):874-882 |
| abstractText | BACKGROUND/AIMS: beta-Klotho, a transmembrane protein expressed in several tissues including the brain and the kidney, is critically important for inhibition of 1,25(OH)2D3 formation by FGF23. The extracellular domain of Klotho protein could be cleaved off, thus being released into blood or cerebrospinal fluid. Soluble klotho is a beta-glucuronidase participating in the regulation of several ion channels and carriers. The present study explored the effect of beta-Klotho protein on the peptide transporters PEPT1 and PEPT2. METHODS: cRNA encoding PEPT1 or PEPT2 was injected into Xenopus laevis oocytes and glycine-glycine (2 mM)-induced inward current (IGly) taken as measure of glycine-glycine transport. Measurements were made without or with prior 24 h treatment with soluble beta-Klotho protein (30 ng/ml) in the absence and presence of beta-glucuronidase inhibitor D-saccharic acid 1,4-lactone monohydrate (DSAL,10 microM). Ussing chamber experiments were employed to determine electrogenic peptide transport across intestinal epithelia of klotho deficient (kl-/-) and corresponding wild type (kl+/+) mice. RESULTS: IGly was observed in PEPT1 and in PEPT2 expressing oocytes but not in water injected oocytes. In both, PEPT1 and PEPT2 expressing oocytes IGly was significantly decreased by treatment with soluble beta-Klotho protein. As shown for PEPT1, beta-klotho protein decreased significantly the maximal transport rate without significantly modifying the affinity of the carrier. The effect of beta-Klotho on PEPT1 was reversed by DSAL. Intestinal IGly was significantly larger in kl-/- than in kl+/+ mice. CONCLUSION: beta-Klotho participates in the regulation of the peptide transporters PEPT1 and PEPT2. |
