Parathyroid hormone-dependent endocytosis of renal type IIc Na-Pi cotransporter.
Hereditary hypophosphatemic rickets with hypercalciuria results from mutations of the renal type IIc Na-P(i) cotransporter gene, suggesting that the type IIc transporter plays a prominent role in renal phosphate handling. The goal of the present study was to investigate the regulation of the type IIc Na-P(i) cotransporter by parathyroid hormone (PTH). Type IIc Na-P(i) cotransporter levels were markedly increased in thyroparathyroidectomized (TPTX) rats. Four hours after administration of PTH, type IIc transporter protein levels were markedly decreased in the apical membrane fraction but recovered to baseline levels at 24 h. Immunohistochemical analyses demonstrated the presence of the type IIc transporter in the apical membrane and subapical compartments in the proximal tubular cells in TPTX animals. After administration of PTH, the intensity of immunoreactive signals in apical and subapical type IIc transporter decreased in the renal proximal tubular cells in TPTX rats. Colchicine completely blocked the internalization of the type IIc transporter. In addition, leupeptin prevented the PTH-mediated degradation of the type IIa transporter in lysosomes but had no effect on PTH-mediated degradation of the lysosomal type IIc transporter. In PTH-treated TPTX rats, the internalization of the type IIc transporter occurred after administration of PTH(1-34) (PKA and PKC activator) or PTH(3-34) (PKC activator). Thus the present study demonstrated that PTH is a major hormonal regulator of the type IIc Na-P(i) cotransporter in renal proximal tubules.
Segawa
Hiroko
H
Dept. of Molecular Nutrition, Institution of Health Biosciences, The Univ. of Tokushima Graduate School, Kuramoto-Cho 3, Tokushima City 770-8503, Japan.
Yamanaka
Setsuko
S
Onitsuka
Akemi
A
Tomoe
Yuka
Y
Kuwahata
Masashi
M
Ito
Mikiko
M
Taketani
Yutaka
Y
Miyamoto
Ken-ichi
K
D000818:Animals; D015152:Blotting, Northern; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000502:physiology*; D016105:Parathyroidectomy; D010446:Peptide Fragments / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa / Q000378:metabolism*; D013965:Thyroidectomy
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D010710:Phosphates; C493556:Slc34a1 protein, rat; D050613:Sodium-Phosphate Cotransporter Proteins, Type IIa; C031617:parathyroid hormone (3-34); D012313:RNA