Parathyroid hormone leads to the lysosomal degradation of the renal type II Na/Pi cotransporter

Markus F. Pfister, Isabelle Ruf, Gerti Stange, Urs Ziegler, Eleanor Lederer, Jürg Biber, Heini Murer

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Abstract

We have studied the involvement of proteolytic pathways in the regulation of the Na/Pi cotransporter type II by parathyroid hormone (PTH) in opossum kidney cells. Inhibition of lysosomal degradation (by leupeptin, ammonium chloride, methylamine, chloroquine, L-methionine methyl ester) prevented the PTH-mediated degradation of the transporter, whereas inhibition of the proteasomal pathway (by lactacystin) did not. Moreover it was found (i) that whereas lysosomal inhibitors prevented the PTH-mediated degradation of the transporter they did not prevent the PTH-mediated inhibition of the Na/Pi cotransport and (ii) that treating opossum kidney cells with lysosomal inhibitors led to an increased expression of the transporter without any concomitant increase in the Na/Pi cotransport. Further analysis by subcellular fractionation and morphological techniques showed (i) that the Na/Pi cotransporter is constitutively transported to and degraded within late endosomes/lysosomes and (ii) that PTH leads to the increased degradation of the transporter in late endosomes/lysosomes.

Original languageEnglish (US)
Pages (from-to)1909-1914
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number4
DOIs
StatePublished - Feb 17 1998
Externally publishedYes

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