Open AccessParathyroid hormone leads to the lysosomal degradation of the renal type II Na/P i cotransporter
Author(s) -
M. Pfister,
Isabelle Ruf,
Gerti Stange,
Urs Ziegler,
Eleanor Lederer,
Jürg Biber,
Heini Murer
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.4.1909
Subject(s) - cotransporter , lactacystin , endosome , leupeptin , parathyroid hormone , chemistry , endocrinology , kidney , medicine , biochemistry , bafilomycin , biology , enzyme , proteasome , calcium , receptor , proteasome inhibitor , organic chemistry , protease , sodium , apoptosis , autophagy
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.