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Volume 272, Number 32, Issue of August 8, 1997 pp. 20125-20130
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Parathyroid Hormone-dependent Degradation of Type II Na+/Pi Cotransporters

(Received for publication, September 12, 1996, and in revised form, February 28, 1997)

Markus F. Pfister Dagger , Eleanor Lederer § , Judith Forgo Dagger , Urs Ziegler , Marius Lötscher Dagger , Elgar S. Quabius Dagger , Jürg Biber Dagger and Heini Murer Dagger

From the Institute of Dagger  Physiology and  Anatomy, University of Zurich, CH-8057 Zurich, Switzerland and the § Department of Medicine, Division of Nephrology, University of Louisville, Louisville, Kentucky 40292

Parathyroid hormone (PTH) inhibits proximal tubular brush border membrane Na+/Pi cotransport activity; this decrease in the transport activity was found to be associated with a decrease in type II Na+/Pi cotransporter protein content in rat brush border membranes. In the present study we investigated the PTH-dependent regulation of the type II Na+/Pi cotransporter in opossum kidney cells, a previously established model to study cellular mechanisms involved in the regulation of proximal tubular Na+/Pi cotransport. We transfected opossum kidney cells with a cDNA coding for NaPi-2 (rat renal type II Na+/Pi cotransporter). This allowed the study of PTH-dependent regulation of the transfected NaPi-2 and of the corresponding intrinsic cotransporter (NaPi-4). The results show (i) that the intrinsic and the transfected cotransporters are functionally (transport) and morphologically (immunofluorescence) localized at the apical membrane, (ii) that the intrinsic as well as the transfected Na+/Pi cotransport activities are inhibited by PTH, (iii) that PTH leads to a retrieval of both cotransporters from the apical membrane, (iv) that both cotransporters are rapidly degraded in response to PTH, and (v) that the reappearance/recovery of type II Na+/Pi cotransporter protein and function from PTH inhibition requires de novo protein synthesis. These results document that PTH leads to a removal of type II Na+/Pi cotransporters from the apical membrane and to their subsequent degradation.


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