PARATHYROID-HORMONE LEADS TO THE LYSOSOMAL DEGRADATION OF THE RENAL TYPE-II NA P-I COTRANSPORTER/

We have studied the involvement of proteolytic pathways in the regulat ion of the Na/P-i cotransporter type II by parathyroid hormone (PTH) i n opossum kidney cells, Inhibition of lysosomal degradation (by leupep tin, ammonium chloride, methylamine, chloroquine, L-methionine methyl ester) prevented the PTH-mediated degradation of the transporter, wher eas inhibition of the proteasomal pathway (by lactacystin) did not, Mo reover it was found (i) that whereas lysosomal inhibitors prevented th e PTH-mediated degradation of the transporter they did not prevent til e PTH-mediated inhibition of the Na/P-i cotransport and (iii) that tre ating opossum kidney cells with lysosomal inhibitors led to an increas ed expression of the transporter without ally concomitant increase in the Na/P-i cotransport, Further analysis by subcellular fractionation and morphological techniques showed (i) that the Na/P-i cotransporter is constitutively transported to and degraded within late endosomes/ly sosomes and (ii) that PTH leads to the increased degradation of the tr ansporter in late endosomes/lysosomes.