Molecular effects of volume expansion on the renal sodium phosphate cotransporter.
BACKGROUND: Volume Expansion (VE) results in both natriuresis and a phosphaturia. In previous studies, Sprague-Dawley rats were infused with a modified saline solution. The expansion procedure resulted in a 70% increase in the phosphorylation of a 72 kDa proximal tubular brush border membrane (BBM) protein. In recent experiments, Sprague-Dawley rats were subjected to the same short term VE. For both control and VE animals, brush border membrane vesicles (BBMV) were obtained. METHODS AND RESULTS: Mass spectrometry of 3 proteins in the size range of our phosphoprotein resulted in the identification of ezrin/villin2, moesin, and PDZ domain-containing 1 (PDZ-dc1). Diphor-1 (currently renamed PDZ-dc1) is involved in regulation of the type II Na/Pi cotransporter. Ezrin and moesin are membrane-cytoskeletal linking proteins that are involved in the regulation of the sodium-hydrogen exchanger (NHE3) via interactions with another PDZ protein identified as sodium-hydrogen exchanger regulatory factor (EBP50, NHERF). Ezrin, moesin, and PDZ-dc1 protein levels were not increased following short term VE. Two-dimensional electrophoresis of our phosphorylated BBM proteins, followed by MALDI/MS analysis resulted in the identification of a protein mixture containing ezrin/moesin, alkaline phosphatase, and an unknown protein. Based on Western and immunoprecipitation data for ezrin, moesin, and PDZ-dc1 we believe that it is unlikely that our phosphoprotein is any of these 3 proteins. Parallels between NHE3 regulation (through EBP50/ ERM proteins) and Na/Pi cotransporter regulation (through PDZ-dc1/ ERM proteins) may be drawn. CONCLUSION: These changes in proximal Na/Pi cotransport may involve a signal transduction cascade including PDZ-dc1, ezrin, moesin, our phosphoprotein, and possibly other proteins.[1]References
- Molecular effects of volume expansion on the renal sodium phosphate cotransporter. Puschett, J.B., Whitbred, J., Ianosi-Irimie, M., Vu, H.V., Rabon, E., Robinson, J., Deininger, P. Am. J. Med. Sci. (2003) [Pubmed]
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