Internalization of proximal tubular type II Na-P(i) cotransporter by PTH: immunogold electron microscopy.
Physiological/pathophysiological alterations in proximal tubular P(i) reabsorption are associated with an altered brush-border membrane (BBM) expression of type II Na-P(i) cotransporter molecules. Reduction is achieved by an internalization and lysosomal degradation and an increase in P(i) reabsorption by new synthesis and BBM insertion of type II Na-P(i) cotransporters. In the present study, we investigated by immunohistochemistry and immunogold electron microscopy the routing of internalized rat type II Na-P(i) cotransporters (NaPi-2). In kidney of rats on a chronic low-P(i) diet, NaPi-2 is mainly localized in the BBM, in cisterns of the Golgi apparatus and sparsely also in large endocytotic vacuoles and lysosomes. Fifteen minutes after the injection of the 1-34 analog of parathyroid hormone (PTH), the amount of NaPi-2 was decreased in the BBM and increased in endocytotic vesicles. NaPi-2 molecules colocalized with horseradish peroxidase injected prior to the injection of PTH. Vesicles labeled for NaPi-2 were occasionally also labeled for clathrin or the adaptor protein AP2. We conclude that NaPi-2 molecules enter the subapical compartment from where NaPi-2-containing vesicles are segregated off and directed to the lysosomes. A clathrin-mediated pathway may contribute to the PTH-induced internalization of NaPi-2.
Traebert
M
M
Institute of Physiology, University of Zurich, Zurich CH-8057, Switzerland.
Roth
J
J
Biber
J
J
Murer
H
H
Kaissling
B
B
D033962:Adaptor Protein Complex 2; D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006735:Horseradish Peroxidase / Q000008:administration & dosage; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters
D033962:Adaptor Protein Complex 2; D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D002966:Clathrin; D008565:Membrane Proteins; D010281:Parathyroid Hormone; D050608:Sodium-Phosphate Cotransporter Proteins; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D027981:Symporters; D006735:Horseradish Peroxidase