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Abstract: TH-PO638

Ezrin Regulates Multiple Solutes Reabsorption via the Regulation of Membrane Protein Localization in the Proximal Tubules

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1300 Health Maintenance, Nutrition, and Metabolism

Authors

  • Hatano, Ryo, Chiba University, Chiba, Japan
  • Kawaguchi, Kotoku, Ritsumeikan University, Kusatsu, Japan
  • Miki, Takashi, Chiba University, Graduate School of Medicine, Chiba, Japan
  • Asano, Shinji, Ritsumeikan University, Kusatsu, Japan
Background

Ezrin is a member of ERM (ezrin-radixin-moesin) proteins and works as a cross-linker between membrane protein and actin cytoskeleton. In kidneys, intense expression of ezrin is observed in proximal tubules, and it is postulated that ezrin plays important roles in tubular solute reabsorption via the regulation of apical membrane localization of several transporters. We previously reported that ezrin knockdown (Vil2kd/kd) mice show hypophosphatemia due to mislocalization of Na+dependent phosphate transporters and its scaffold protein, Na+/H+exchanger regulatory factor 1 (NHERF1). However, we haven’t investigated the influence of loss of ezrin on the membrane localizations of other transporters.

Methods

We performed a comprehensive proteomic analysis of renal brush border membrane vesicles (BBMVs) of proximal tubules from Wild type (WT) and Vil2kd/kd mice in this study. We also measured the plasma concentration and urinary excretion of nutrition including amino acids, glucose, and low molecular weight protein.

Results

We identified totally 1,412 proteins including 18.8 % of membrane integral proteins from WT and Vil2kd/kd mice. Scaffold proteins including NHERF1 and PDZK1 were significantly decreased in Vil2kd/kd mice. Several transporters including Slc5a1, Slc5a11, Slc22a4 and Slc22a5 showed marginally significant reduction (0.05 < p < 0.1). We also found that BBMV localizations of several other solute transporters associated with the reabsorptions of amino acids, glucose, and organic anions were totally decreased in Vil2kd/kd mice, suggesting that Vil2kd/kd mice exhibit the phenotype of Fanconi syndrome, which is accompanied with massive urinary solute waste. On the other hand, expressions of several proteins associated with actin remodeling, and endocytosis were increased in Vil2kd/kd BBMVs. Vil2kd/kd mice showed defective endocytosis of FITC-labeled β2-microglobulin similar to Fanconi syndrome model mice.

Conclusion

These results suggest that ezrin plays important roles in the regulation of several membrane transporter localizations in the proximal tubules.

Funding

  • Government Support - Non-U.S.