Molecular Characteristics of Phosphate Transporters and Their Regulation

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

A key process in overall Pi-homeostasis is renal proximal tubular reabsorption of inorganic phosphate (Pi), which involves secondary active sodium/phosphate (Na+/Pi) cotransport reabsorption at the brush border membrane. Among the two different molecularly identified Na+/Pi cotransporters, the type-IIa Na+/Pi cotransporter (NaPi-IIa) accounts for up to 70% of brush border membrane transport. Regulation of renal Pi reabsorption centers around brush border membrane insertion and retrieval of transporter protein under the influence of hormonal and nonhormonal factors. Immunohistochemical and fluorescence techniques have provided new insights into the tissue distribution and the regulation processes. The intrinsic electrogenicity of NaPi-IIa, has allowed detailed studies of the transport kinetics of NaPi-IIa and, combined with mutagenesis methods, structure-function information at the protein level is emerging.

Related collections

Most cited references 22

Record: found
Abstract: found
Article: not found

Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities.

Jennifer Beck, H Ozawa, A Karaplis … (1998)

Npt2 encodes a renal-specific, brush-border membrane Na+-phosphate (Pi) cotransporter that is expressed in the proximal tubule where the bulk of filtered Pi is reabsorbed. Mice deficient in the Npt2 gene were generated by targeted mutagenesis to define the role of Npt2 in the overall maintenance of Pi homeostasis, determine its impact on skeletal development, and clarify its relationship to autosomal disorders of renal Pi reabsorption in humans. Homozygous mutants (Npt2(-/-)) exhibit increased urinary Pi excretion, hypophosphatemia, an appropriate elevation in the serum concentration of 1,25-dihydroxyvitamin D with attendant hypercalcemia, hypercalciuria and decreased serum parathyroid hormone levels, and increased serum alkaline phosphatase activity. These biochemical features are typical of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a Mendelian disorder of renal Pi reabsorption. However, unlike HHRH patients, Npt2(-/-) mice do not have rickets or osteomalacia. At weaning, Npt2(-/-) mice have poorly developed trabecular bone and retarded secondary ossification, but, with increasing age, there is a dramatic reversal and eventual overcompensation of the skeletal phenotype. Our findings demonstrate that Npt2 is a major regulator of Pi homeostasis and necessary for normal skeletal development.

0 comments Cited 118 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine.

H Hilfiker, O Hattenhauer, M Traebert … (1998)

An isoform of the mammalian renal type II Na/Pi-cotransporter is described. Homology of this isoform to described mammalian and nonmammalian type II cotransporters is between 57 and 75%. Based on major diversities at the C terminus, the new isoform is designed as type IIb Na/Pi-cotransporter. Na/Pi-cotransport mediated by the type IIb cotransporter was studied in oocytes of Xenopus laevis. The results indicate that type IIb Na/Pi-cotransport is electrogenic and in contrast to the renal type II isoform of opposite pH dependence. Expression of type IIb mRNA was detected in various tissues, including small intestine. The type IIb protein was detected as a 108-kDa protein by Western blots using isolated small intestinal brush border membranes and by immunohistochemistry was localized at the luminal membrane of mouse enterocytes. Expression of the type IIb protein in the brush borders of enterocytes and transport characteristics suggest that the described type IIb Na/Pi-cotransporter represents a candidate for small intestinal apical Na/Pi-cotransport.

0 comments Cited 69 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Conformational changes couple Na+ and glucose transport.

Viviana Gallardo, Stephen E Wright, Bruce Hirayama … (1998)

The mechanism by which cotransport proteins couple their substrates across cell membranes is not known. A commonly proposed model is that cotransport results from ligand-induced conformational transitions that change the accessibility of ligand-binding sites from one side of the membrane to the other. To test this model, we have measured the accessibility of covalent probes to a cysteine residue (Q457C) placed in the putative sugar-translocation domain of the Na+/glucose cotransporter (SGLT1). The mutant protein Q457C was able to transport sugar, but transport was abolished after alkylation by methanethiosulfonate reagents. Alkylation blocked sugar translocation but not sugar binding. Accessibility of Q457C to alkylating reagents required external Na+ and was blocked by external sugar and phlorizin. The voltage dependence of accessibility was directly correlated with the presteady-state charge movement of SGLT1. Voltage-jump experiments with rhodamine-6-maleimide-labeled Q457C showed that the time course and level of changes in fluorescence closely followed the presteady-state charge movement. We conclude that conformational changes are responsible for the coupling of Na+ and sugar transport and that Q457 plays a critical role in sugar translocation by SGLT1.

0 comments Cited 27 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (publisher-id): EXN

Journal ID (nlm-ta): Nephron Exp Nephrol

Journal ID (doi): 10.1159/issn.1660-2129

Title: Cardiorenal Medicine

Publisher: S. Karger AG

ISBN: 978-3-8055-7143-2

ISBN: 978-3-318-00633-9

ISSN (Electronic): 1660-2129

Publication date Subscription-year: 2000

Publication date (Print): December 2000

Publication date (Electronic): 15 September 2000

Volume: 8

Issue: 6

Pages: 366-375

Affiliations

Institute of Physiology, University of Zurich, Switzerland

Article

Publisher ID: 20691 Other ID: Exp Nephrol 2000;8:366–375

DOI: 10.1159/000020691

PubMed ID: 11014934

SO-VID: 27e21e42-705f-429d-8aab-5a6878bcef9d

License:

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

Submit here before July 31, 2024

Molecular Characteristics of Phosphate Transporters and Their Regulation

Read this article at

Abstract

Related collections

Karger: Nephrology

Most cited references 22

Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities.

Characterization of a murine type II sodium-phosphate cotransporter expressed in mammalian small intestine.

Conformational changes couple Na+ and glucose transport.

Author and article information

Journal

Affiliations

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 185

Cited by 3

Most referenced authors 591