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The membrane cytoskeletal crosslinker ezrin is essential for the regulation of phosphate and calcium homeostasis
Author(s) -
Asano Shinji,
Hatano Ryo,
Matsumoto Yosuke,
Segawa Hiroko,
Miyamoto Kenichi,
Matsubara Mitsunobu
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.912.5
Subject(s) - ezrin , reabsorption , chemistry , homeostasis , medicine , endocrinology , kidney , apical membrane , microbiology and biotechnology , cytoskeleton , membrane , biology , biochemistry , cell
Ezrin is a cross‐linker between the plasma membrane proteins and actin cytoskeleton. In the kidney, ezrin is mainly localized at brush border membrane of proximal tubules with a scaffolding protein, Na + /H + exchanger regulatory factor (NHERF) 1. NHERF1 interacts with Na + /phosphate (P i ) cotransporter Npt2a. We focused on the physiological role of ezrin in the renal P i reabsorption by using ezrin knockdown mice ( Vil2 kd/kd ). The Vil2 kd/kd mice exhibited hypophosphatemia, hypocalcemia, and osteomalacia. The reduced plasma concentration of P i was attributed to the defective urinary P i reabsorption. Immunofluorescence staining and immunoblotting revealed that the Npt2a and NHERF1 expressions at apical membrane of proximal tubules were markedly reduced in the kidney of Vil2 kd/kd mice. On the other hand, urinary loss of Ca 2+ was not observed in Vil2 kd/kd mice. Plasma concentration of 1,25‐dihydroxyvitamin D was elevated following reduced plasma P i level. Furthermore, bone mineral density in tibiae was significantly lowered in the adult and young Vil2 kd/kd mice. These results suggest that ezrin is required for the regulation of systemic P i homeostasis in vivo .