Acute regulation of Na+/H+ exchanger NHE3 by parathyroid hormone via NHE3 phosphorylation and dynamin-dependent endocytosis

Roberto Collazo, Lingzhi Fan, Ming C Hu, Hui Zhao, Michael R. Wiederkehr, Orson W Moe

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Abstract

Parathyroid hormone (PTH) is a potent inhibitor of mammalian renal proximal tubule Na+ transport via its action on the apical membrane Na+/H+ exchanger NHE3. In the opossum kidney cell line, inhibition of NHE3 activity was detected from 5 to 45 min after PTH addition. Increase in NHE3 phosphorylation on multiple serines was evident after 5 min of PTH, but decrease in surface NHE3 antigen was not detectable until after 30 min of PTH. The decrease in surface NHE3 antigen was due to increased NHE3 endocytosis. When endocytic trafficking was arrested with a dominant negative dynamin mutant (K44A), the early inhibition (5 min) of NHE3 activity by PTH was not affected, whereas the late inhibition (30 min) and decreased surface NHE3 antigen induced by PTH were abrogated. We conclude that PTH acutely inhibits NHE3 activity in a biphasic fashion by NHE3 phosphorylation followed by dynamin-dependent endocytosis.

Original languageEnglish (US)
Pages (from-to)31601-31608
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number41
StatePublished - Oct 13 2000

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Dynamins
Sodium-Hydrogen Antiporter
Phosphorylation
Endocytosis
Parathyroid Hormone
Surface Antigens
Antigens
Opossums
Proximal Kidney Tubule
Serine
Cells
Membranes
Kidney
Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

Acute regulation of Na+/H+ exchanger NHE3 by parathyroid hormone via NHE3 phosphorylation and dynamin-dependent endocytosis. / Collazo, Roberto; Fan, Lingzhi; Hu, Ming C; Zhao, Hui; Wiederkehr, Michael R.; Moe, Orson W.

In: Journal of Biological Chemistry, Vol. 275, No. 41, 13.10.2000, p. 31601-31608.

Research output: Contribution to journalArticle

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AU - Fan, Lingzhi

AU - Hu, Ming C

AU - Zhao, Hui

AU - Wiederkehr, Michael R.

AU - Moe, Orson W

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N2 - Parathyroid hormone (PTH) is a potent inhibitor of mammalian renal proximal tubule Na+ transport via its action on the apical membrane Na+/H+ exchanger NHE3. In the opossum kidney cell line, inhibition of NHE3 activity was detected from 5 to 45 min after PTH addition. Increase in NHE3 phosphorylation on multiple serines was evident after 5 min of PTH, but decrease in surface NHE3 antigen was not detectable until after 30 min of PTH. The decrease in surface NHE3 antigen was due to increased NHE3 endocytosis. When endocytic trafficking was arrested with a dominant negative dynamin mutant (K44A), the early inhibition (5 min) of NHE3 activity by PTH was not affected, whereas the late inhibition (30 min) and decreased surface NHE3 antigen induced by PTH were abrogated. We conclude that PTH acutely inhibits NHE3 activity in a biphasic fashion by NHE3 phosphorylation followed by dynamin-dependent endocytosis.

AB - Parathyroid hormone (PTH) is a potent inhibitor of mammalian renal proximal tubule Na+ transport via its action on the apical membrane Na+/H+ exchanger NHE3. In the opossum kidney cell line, inhibition of NHE3 activity was detected from 5 to 45 min after PTH addition. Increase in NHE3 phosphorylation on multiple serines was evident after 5 min of PTH, but decrease in surface NHE3 antigen was not detectable until after 30 min of PTH. The decrease in surface NHE3 antigen was due to increased NHE3 endocytosis. When endocytic trafficking was arrested with a dominant negative dynamin mutant (K44A), the early inhibition (5 min) of NHE3 activity by PTH was not affected, whereas the late inhibition (30 min) and decreased surface NHE3 antigen induced by PTH were abrogated. We conclude that PTH acutely inhibits NHE3 activity in a biphasic fashion by NHE3 phosphorylation followed by dynamin-dependent endocytosis.

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