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The renal Na+/phosphate cotransporter NaPi-IIa is internalized via the receptor-mediated endocytic route in response to parathyroid hormone.


Bacic, D; Lehir, M; Biber, J; Kaissling, B; Murer, H; Wagner, C A (2006). The renal Na+/phosphate cotransporter NaPi-IIa is internalized via the receptor-mediated endocytic route in response to parathyroid hormone. Kidney International, 69(3):495-503.

Abstract

The major renal Na(+)/phosphate cotransporter, NaPi-IIa, is regulated by a number of factors including parathyroid hormone (PTH), dopamine, and dietary phosphate intake. PTH induces the acute internalization of NaPi-IIa from the brush border membrane (BBM) and its routing to and subsequent degradation in lysosomes. Previous work indicated that megalin, part of the apical receptor-mediated endocytic apparatus, may play a role in the PTH-induced removal of NaPi-IIa. Here we examined in rats the time-dependent internalization route of NaPi-IIa after acute PTH application using immunohistochemistry and markers of several endocytic compartments. NaPi-IIa removal from the BBM was detectable as early as 5 min after PTH injection. After 10-15 min, NaPi-IIa was localized in subapical compartments positive for clathrin. Shortly thereafter, NaPi-IIa appeared in endosomes stained for EEA1 (early endosomal antigen 1). After 45-60 min, NaPi-IIa was found in late endosomes/lysosomes marked with lgp120. In contrast, no change in the subcellular localization of megalin and the Na(+)/H(+) exchanger NHE3 was detected up to 60 min after PTH injection. To further characterize the internalization route, insulin, as a marker for receptor-mediated endocytosis, and horseradish peroxidase (HRP) and fluorescein isothiocyanate (FITC)-dextran (10 kDa), as markers for fluid-phase mediated endocytosis, were used. NaPi-IIa colocalized with insulin 5-30 min after PTH injection but did not overlap with HRP or FITC-dextran. These results demonstrate a distinct internalization route of NaPi-IIa in response to acute PTH application that may involve the receptor-mediated endocytic pathway including clathrin-coated vesicles and EEA1-positive early endosomes, and routes NaPi-IIa to lysosomes for degradation.

The major renal Na(+)/phosphate cotransporter, NaPi-IIa, is regulated by a number of factors including parathyroid hormone (PTH), dopamine, and dietary phosphate intake. PTH induces the acute internalization of NaPi-IIa from the brush border membrane (BBM) and its routing to and subsequent degradation in lysosomes. Previous work indicated that megalin, part of the apical receptor-mediated endocytic apparatus, may play a role in the PTH-induced removal of NaPi-IIa. Here we examined in rats the time-dependent internalization route of NaPi-IIa after acute PTH application using immunohistochemistry and markers of several endocytic compartments. NaPi-IIa removal from the BBM was detectable as early as 5 min after PTH injection. After 10-15 min, NaPi-IIa was localized in subapical compartments positive for clathrin. Shortly thereafter, NaPi-IIa appeared in endosomes stained for EEA1 (early endosomal antigen 1). After 45-60 min, NaPi-IIa was found in late endosomes/lysosomes marked with lgp120. In contrast, no change in the subcellular localization of megalin and the Na(+)/H(+) exchanger NHE3 was detected up to 60 min after PTH injection. To further characterize the internalization route, insulin, as a marker for receptor-mediated endocytosis, and horseradish peroxidase (HRP) and fluorescein isothiocyanate (FITC)-dextran (10 kDa), as markers for fluid-phase mediated endocytosis, were used. NaPi-IIa colocalized with insulin 5-30 min after PTH injection but did not overlap with HRP or FITC-dextran. These results demonstrate a distinct internalization route of NaPi-IIa in response to acute PTH application that may involve the receptor-mediated endocytic pathway including clathrin-coated vesicles and EEA1-positive early endosomes, and routes NaPi-IIa to lysosomes for degradation.

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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:1 February 2006
Deposited On:11 Feb 2008 12:22
Last Modified:05 Apr 2016 12:18
Publisher:Nature Publishing Group
ISSN:0085-2538
Publisher DOI:10.1038/sj.ki.5000148
PubMed ID:16514432

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