| First Author | Fujii T | Year | 2019 |
| Journal | Clin Exp Nephrol | Volume | 23 |
| Issue | 7 | Pages | 898-907 |
| PubMed ID | 30895530 | Mgi Jnum | J:294470 |
| Mgi Id | MGI:6456505 | Doi | 10.1007/s10157-019-01725-6 |
| Citation | Fujii T, et al. (2019) Role of the putative PKC phosphorylation sites of the type IIc sodium-dependent phosphate transporter in parathyroid hormone regulation. Clin Exp Nephrol 23(7):898-907 |
| abstractText | BACKGROUND: Injection of parathyroid hormone (PTH) rapidly stimulates renal Pi excretion, in part by downregulating NaPi-IIa (Npt2a/SLC34A1) and NaPi-IIc (Npt2c/SLC34A3) transporters. The mechanisms underlying the effects of PTH on NaPi-IIc are not fully elucidated. METHODS: We analyzed the effect of PTH on inorganic phosphate (Pi) reabsorption in Npt2a(-/-) mice to eliminate the influence of Npt2a on renal Pi reabsorption. In opossum kidney (OK) cells and Xenopus oocytes, we investigated the effect of NaPi-IIc transporter phosphorylation. Studies of mice with mutations of NaPi-IIc protein in which serine and threonine were replaced with either alanine (A), which prevents phosphorylation, or aspartic acid (D), which mimics the charged state of phosphorylated NaPi-IIc, were also performed to evaluate the involvement of phosphorylation in the regulation of transport function. RESULTS: The Npt2a(-/-) experiments showed that PTH administration rapidly inactivated NaPi-IIc function in the apical membrane of proximal tubular cells. Analysis of mutant proteins (S71, S138, T151, S174, T583) at putative protein kinase C sites, revealed that S138 markedly suppressed the function and cellular expression of mouse NaPi-IIc in Xenopus oocytes and OK cells. In addition, 138D had a short half-life compared with wild-type protein. CONCLUSIONS: The present study suggests that acute regulation of NaPi-IIc protein by PTH is involved in the inactivation of Na(+)-dependent Pi cotransporter activity and that phosphorylation of the transporter is involved in the rapid modification. |
