Ezrin promotes functional expression and parathyroid hormone-mediated regulation of the sodium-phosphate cotransporter 2a in LLC-PK1 cells

American Journal of Physiology. Renal Physiology
Matthew J Mahon

Abstract

The sodium-phosphate cotransporter 2a (NPT2a) is the principal phosphate transporter expressed in the brush border of renal proximal tubules and is downregulated by parathyroid hormone (PTH) through an endocytic mechanism. Apical membrane expression of NPT2a is dependent on interactions with the sodium-hydrogen exchanger regulatory factor 1 (NHERF-1). An LLC-PK1 renal cell line stably expressing the PTH receptor (PTH1R) and NHERF-1, termed B28-N1, fails to functionally express NPT2a. In B28-N1 cells, NHERF-1 and NPT2a are inappropriately localized to the cytoplasm. Ezrin, in the activated state, is capable at linking NHERF-1-assembled complexes to the actin cytoskeleton. Early-passage LLC-PK1 cells stably transfected with either empty vector or wild-type ezrin express a comparable level of the active, T567 phosphorylated form of ezrin and are capable of functionally expressing NPT2a. Colocalization of the PTH1R, NPT2a, and ezrin exists and is prominently associated with actin-containing microvilli in apical domains of these cells. Upon PTH treatment, the PTH1R, NPT2a, NHERF-1, and ezrin colocalize to endocytic vesicles and NPT2a-dependent phosphate uptake is markedly inhibited. LLC-PK1 cells expressing the constitutively active...Continue Reading

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Citations

Jan 1, 2010·The Journal of Biological Chemistry·Shibani BhattacharyaZimei Bu
Sep 25, 2009·American Journal of Physiology. Cell Physiology·Judith BlaineMoshe Levi
Jan 23, 2009·American Journal of Physiology. Cell Physiology·Anne D M RiquierAlicia A McDonough
Oct 30, 2009·American Journal of Physiology. Renal Physiology·Anne D M Riquier-BrisonAlicia A McDonough
Oct 2, 2009·American Journal of Physiology. Renal Physiology·Edward J WeinmanMark Donowitz
Jul 16, 2013·Biochimica Et Biophysica Acta·Mohamad AdadaLina M Obeid
Jul 14, 2009·Journal of Molecular Biology·Jianquan LiZimei Bu
Jan 25, 2013·American Journal of Physiology. Renal Physiology·Rebecca D MurrayEleanor D Lederer
Nov 24, 2017·Journal of Lipid Research·Thomas G MorrisJacqueline Ohanian

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