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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Professor Emeritus of Psychiatry and Behavioral Sciences
Protein phosphorylation controls a wide range of physiological processes in mammalian tissues. Phosphorylation state of cellular proteins is controlled by the opposing actions of protein kinases and phosphatases that are regulated by hormones, neurotransmitters, growth factors and other environmental cues. Our research attempts to understand the communication between protein kinases and phosphatases that dictates cellular protein phosphorylation and the cell's response to hormones. Over the