Dynamics of PTH-induced disassembly of Npt2a/NHERF-1 complexes in living OK cells.
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Parathyroid hormone (PTH) inhibits the reabsorption of phosphate in the renal proximal tubule by disrupting the binding of the sodium-dependent phosphate transporter 2A (Npt2a) to the adapter protein sodium-hydrogen exchanger regulatory factor-1 (NHERF-1), a process initiated by activation of protein kinase C (PKC). To gain additional insights into the dynamic sequence of events, the time course of these responses was studied in living opossum kidney (OK) cells. Using a FRET-based biosensor, we found that PTH activated intracellular PKC within seconds to minutes. In cells expressing GFP-Npt2a and mCherry-NHERF, PTH did not affect the relative abundance of NHERF-1 but there was a significant and time-dependent decrease in the Npt2a/NHERF-1 ratio. The half-time to maximal dissociation was 15 to 20 min. By contrast, PTH had no effect on the fluorescence ratio for GFP-ezrin compared with mCherry-NHERF-1 at the apical surface. These experiments establish that PTH treatment of proximal tubule OK cells leads to rapid activation of PKC with the subsequent dissociation of Npt2a/NHERF-1 complexes. The association of NHERF-1 with Ezrin and their localization at the apical membrane, however, was unperturbed by PTH, thereby enabling the rapid recruitment and membrane reinsertion of Npt2a and other NHERF-1 targets on termination of the hormone response.
Sodium-Phosphate Cotransporter Proteins, Type IIa
Published Version (Please cite this version)10.1152/ajprenal.00532.2010
Publication InfoBlanpied, Thomas A; Shenolikar, Shirish; Steplock, Deborah; & Weinman, Edward J (2011). Dynamics of PTH-induced disassembly of Npt2a/NHERF-1 complexes in living OK cells. American journal of physiology. Renal physiology, 300(1). pp. F231-F235. 10.1152/ajprenal.00532.2010. Retrieved from https://hdl.handle.net/10161/17232.
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