Ion Channels – Membrane Transport – Integrative Physiology
Kidney International (1998) 54, 1224–1232; doi:10.1046/j.1523-1755.1998.00115.x
Parathyroid hormone and dietary phosphate provoke a lysosomal routing of the proximal tubular Na/Pi-cotransporter type II
Isabelle Keusch, Martin Traebert, Marius Lötscher, Brigitte Kaissling, Heini Murer and Jürg Biber
Institute of Physiology and Institute of Anatomy, University of Zürich, Zürich, Switzerland
Correspondence: Dr J. Biber, Institute of Physiology, University Zürich-Irchel, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland. E-mail: Biber@Physiol.Unizh.CH
Received 4 November 1997; Revised 13 May 1998; Accepted 13 May 1998.
Abstract
Parathyroid hormone and dietary phosphate provoke a lysosomal routing of the proximal tubular Na/Pi-cotransporter type II.
Background
A decrease of proximal tubular reabsorption of phosphate (Pi), which can be provoked by parathyroid hormone (PTH) or by a high Pi-diet, has been shown to correlate with a decrease of the number of type II Na/Pi-cotransporters residing in the brush border membrane. While both PTH and a high Pi-diet lead to an internalization of type II cotransporters, the further cellular routing of internalized cotransporters has not been established unequivocally.
Methods
To prevent lysosomal degradation, rats were treated with leupeptin prior to the injection of PTH or feeding acutely with a high Pi-diet. Kidney cortex were recovered and used for immunohistochemistry. In parallel, brush border membranes and lysosomes were isolated and analyzed by Western blotting.
Results
Under both conditions (PTH and high Pi-diet), a strong overlap of internalized type II cotransporters with the late endosomes/lysosomes was observed by immunohistochemistry. In agreement, the content of type II Na/Pi-cotransporters was increased in lysosomes isolated from the corresponding tissues.
Conclusions
These results suggest that in proximal tubular cells type II Na/Pi-cotransporters internalized due to the action of PTH and acute high Pi-diet are routed to the lysosomes, and likely do not enter a recycling compartment.
Keywords:
transport, phosphate, diet regulation, proximal tubule, lysosomes, parathyroid hormone
