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Functional domains in the renal type IIa Na/P(i)-cotransporter.


Murer, H (2002). Functional domains in the renal type IIa Na/P(i)-cotransporter. Kidney International, 62(2):375-382.

Abstract

The proximal tubular brush border membrane type IIa Na/P(i)-cotransporter is an important element in overall phosphate (Pi) homeostasis. Its regulation is tightly associated with membrane retrieval/reinsertion mechanisms. Specific molecular domains are involved in its internalization (predicted third intracellular loop) and in its apical expression (carboxy-terminus). Regulation and apical expression require a correct ('proximal tubular') cellular context and interaction with specific cellular proteins (scaffolding). Basic cotransport function is via a 3 Na+ to 1 P(i)-coupling ratio, also including the possibility of a Na+-leak, and is strongly affected by changes in pH. This function can be assigned to monomeric transporter molecules. The predicted first intracellular and third extracellular loops contribute important functional characteristics. It is suggested that they may form "re-entrant loops" and thereby a "permeation pore." Sequences in this region determine also pH-sensitivity and affinities in P(i)- and in Na+-interaction, respectively.

Abstract

The proximal tubular brush border membrane type IIa Na/P(i)-cotransporter is an important element in overall phosphate (Pi) homeostasis. Its regulation is tightly associated with membrane retrieval/reinsertion mechanisms. Specific molecular domains are involved in its internalization (predicted third intracellular loop) and in its apical expression (carboxy-terminus). Regulation and apical expression require a correct ('proximal tubular') cellular context and interaction with specific cellular proteins (scaffolding). Basic cotransport function is via a 3 Na+ to 1 P(i)-coupling ratio, also including the possibility of a Na+-leak, and is strongly affected by changes in pH. This function can be assigned to monomeric transporter molecules. The predicted first intracellular and third extracellular loops contribute important functional characteristics. It is suggested that they may form "re-entrant loops" and thereby a "permeation pore." Sequences in this region determine also pH-sensitivity and affinities in P(i)- and in Na+-interaction, respectively.

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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 August 2002
Deposited On:11 Feb 2008 12:23
Last Modified:19 Feb 2018 21:31
Publisher:Nature Publishing Group
ISSN:0085-2538
OA Status:Closed
Publisher DOI:https://doi.org/10.1046/j.1523-1755.2002.00461.x
PubMed ID:12109998

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