Ezrin, a membrane cytoskeletal cross-linker, is essential for the regulation of phosphate and calcium homeostasis

Ryo Hatano, Eiko Fujii, Hiroko Segawa, Kenichi Mukaisho, Mitsunobu Matsubara, Ken Ichi Miyamoto, Takanori Hattori, Hiroyuki Sugihara, Shinji Asano

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Ezrin cross-links plasma membrane proteins with the actin cytoskeleton. In the kidney, ezrin mainly localizes at the brush border membrane of proximal tubules with the scaffolding protein, Na + /H + exchanger regulatory factor (NHERF) 1. NHERF1 interacts with the sodium/phosphate cotransporter, Npt2a. Defects in NHERF1 or Npt2a in mice cause hypophosphatemia. Here we studied the physiological role of ezrin in renal phosphate reabsorption using ezrin knockdown mice (Vil2). These mice exhibit hypophosphatemia, hypocalcemia, and osteomalacia. The reduced plasma phosphate concentrations were ascribed to defects in urinary phosphate reabsorption. Immunofluorescence and immunoblotting indicated a marked reduction in renal Npt2a and NHERF1 expression at the apical membrane of proximal tubules in the knockdown mice. On the other hand, urinary loss of calcium was not found in Vil2 mice. Plasma concentrations of 1,25-dihydroxyvitamin D were elevated following reduced plasma phosphate levels, and mRNA of the vitamin D-dependent TRPV6 calcium channel were significantly increased in the duodenum of knockdown mice. Expression of TRPV6 at the apical membrane, however, was significantly decreased. Furthermore, tibial bone mineral density was significantly lower in both the adult and young Vil2 mice. These results suggest that ezrin is required for the regulation of systemic phosphate and calcium homeostasis in vivo.

Original languageEnglish
Pages (from-to)41-49
Number of pages9
JournalKidney international
Volume83
Issue number1
DOIs
Publication statusPublished - 2013 Jan

Keywords

  • calcium
  • phosphate uptake
  • vitamin D

ASJC Scopus subject areas

  • Nephrology

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