期刊
CLINICAL AND EXPERIMENTAL NEPHROLOGY
卷 23, 期 7, 页码 898-907出版社
SPRINGER
DOI: 10.1007/s10157-019-01725-6
关键词
Opossum kidney cells; Proximal tubule; SLC34A3; Sodium-dependent Pi transport
资金
- Support Center for Advanced Medical Sciences, Tokushima University Graduate School of Biomedical Sciences
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [23689045, 26293204]
- Salt Science Research Foundation (Japan)
- Grants-in-Aid for Scientific Research [23689045, 26293204] Funding Source: KAKEN
BackgroundInjection 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.MethodsWe 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.ResultsThe 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.ConclusionsThe 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.
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