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Rapid downregulation of rat renal Na/Pi cotransporter in response to parathyroid hormone involves microtubule rearrangement
Marius Lötscher, Yvonne Scarpetta, Moshe Levi, Nabil Halaihel, Huamin Wang, Hubert K. Zajicek, Jürg Biber, Heini Murer, Brigitte Kaissling
Marius Lötscher, Yvonne Scarpetta, Moshe Levi, Nabil Halaihel, Huamin Wang, Hubert K. Zajicek, Jürg Biber, Heini Murer, Brigitte Kaissling
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Rapid downregulation of rat renal Na/Pi cotransporter in response to parathyroid hormone involves microtubule rearrangement

Abstract

Renal proximal tubule cells express in their apical brush border membrane (BBM) a Na/Pi cotransporter type IIa that is rapidly downregulated in response to parathyroid hormone (PTH). We used the rat renal Na/Pi cotransporter type IIa (NaPi-2) as an in vivo model to assess early cellular events in the rapid downregulation of this transporter. When rats were treated with PTH for 15 minutes, NaPi-2 abundance in the BBM was decreased. In parallel, transporter accumulated in intracellular vesicles. Concomitantly, microtubules (MTs) were found to form dense bundles of apical-to-basal orientation. After 60 minutes of PTH action, the cells were vastly depleted of NaPi-2, whereas their microtubular cytoskeleton had returned to its normal appearance. Prevention of MT rearrangement by taxol resulted in accumulation of NaPi-2 in the subapical cell portion after 15 minutes and a strong delay in depletion of intracellular transporter after 60 minutes of PTH action. Furthermore, the subapical accumulation of NaPi-2 was associated with the expansion of dense apical tubules of the subapical endocytic apparatus (SEA). Depolymerization of MTs by colchicine likewise caused a retardation of intracellular NaPi-2 depletion. These results suggest that NaPi-2 is downregulated in response to PTH through a rapid endocytic process in 2 separate steps: (a) internalization of the transporter into the SEA, and (b) its delivery to degradative organelles by a trafficking mechanism whose efficiency depends on a taxol-sensitive rearrangement of MTs.

Authors

Marius Lötscher, Yvonne Scarpetta, Moshe Levi, Nabil Halaihel, Huamin Wang, Hubert K. Zajicek, Jürg Biber, Heini Murer, Brigitte Kaissling

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