Water and urea permeation pathways of the human excitatory amino acid transporter EAAT1

R. J. Vandenberg, C. A. Handford, E. M. Campbell, R. M. Ryan, A. J. Yool

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Glutamate transport is coupled to the co-transport of 3 Na+ and 1 H+ followed by the counter-transport of 1 K+. In addition, glutamate and Na+ binding to glutamate transporters generates an uncoupled anion conductance. The human glial glutamate transporter EAAT1 (excitatory amino acid transporter 1) also allows significant passive and active water transport, which suggests that water permeation through glutamate transporters may play an important role in glial cell homoeostasis. Urea also permeates EAAT1 and has been used to characterize the permeation properties of the transporter. We have previously identified a series of mutations that differentially affect either the glutamate transport process or the substrate-activated channel function of EAAT1. The water and urea permeation properties of wild-type EAAT1 and two mutant transporters were measured to identify which permeation pathway facilitates the movement of these molecules. We demonstrate that there is a significant rate of L-glutamate-stimulated passive and active water transport. Both the passive and active L-glutamate-stimulated water transport is most closely associated with the glutamate transport process. In contrast, L-glutamate-stimulated [14C]urea permeation is associated with the anion channel of the transporter. However, there is also likely to be a transporter-specific, but glutamate independent, flux of water via the anion channel.
Original languageEnglish
Pages (from-to)333-340
Number of pages8
JournalBiochemical Journal
Volume439
Issue number2
DOIs
Publication statusPublished - 15 Oct 2011

Fingerprint

Excitatory Amino Acid Transporter 1
Amino Acid Transport Systems
Excitatory Amino Acids
Permeation
Urea
Glutamic Acid
Amino Acid Transport System X-AG
Water
Anions
Active Biological Transport
Neuroglia
Homeostasis

Keywords

  • anion channel
  • glutamate transport
  • urea
  • water transport

Cite this

Water and urea permeation pathways of the human excitatory amino acid transporter EAAT1. / Vandenberg, R. J.; Handford, C. A.; Campbell, E. M.; Ryan, R. M.; Yool, A. J.

In: Biochemical Journal, Vol. 439, No. 2, 15.10.2011, p. 333-340.

Research output: Contribution to journalArticle

Vandenberg, R. J. ; Handford, C. A. ; Campbell, E. M. ; Ryan, R. M. ; Yool, A. J. / Water and urea permeation pathways of the human excitatory amino acid transporter EAAT1. In: Biochemical Journal. 2011 ; Vol. 439, No. 2. pp. 333-340.
@article{34c301d02da641e2b94cc1dd075bfa09,
title = "Water and urea permeation pathways of the human excitatory amino acid transporter EAAT1",
abstract = "Glutamate transport is coupled to the co-transport of 3 Na+ and 1 H+ followed by the counter-transport of 1 K+. In addition, glutamate and Na+ binding to glutamate transporters generates an uncoupled anion conductance. The human glial glutamate transporter EAAT1 (excitatory amino acid transporter 1) also allows significant passive and active water transport, which suggests that water permeation through glutamate transporters may play an important role in glial cell homoeostasis. Urea also permeates EAAT1 and has been used to characterize the permeation properties of the transporter. We have previously identified a series of mutations that differentially affect either the glutamate transport process or the substrate-activated channel function of EAAT1. The water and urea permeation properties of wild-type EAAT1 and two mutant transporters were measured to identify which permeation pathway facilitates the movement of these molecules. We demonstrate that there is a significant rate of L-glutamate-stimulated passive and active water transport. Both the passive and active L-glutamate-stimulated water transport is most closely associated with the glutamate transport process. In contrast, L-glutamate-stimulated [14C]urea permeation is associated with the anion channel of the transporter. However, there is also likely to be a transporter-specific, but glutamate independent, flux of water via the anion channel.",
keywords = "anion channel, glutamate transport, urea, water transport",
author = "Vandenberg, {R. J.} and Handford, {C. A.} and Campbell, {E. M.} and Ryan, {R. M.} and Yool, {A. J.}",
note = "MEDLINE{\circledR} is the source for the MeSH terms of this document.",
year = "2011",
month = "10",
day = "15",
doi = "10.1042/BJ20110905",
language = "English",
volume = "439",
pages = "333--340",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "2",

}

TY - JOUR

T1 - Water and urea permeation pathways of the human excitatory amino acid transporter EAAT1

AU - Vandenberg, R. J.

AU - Handford, C. A.

AU - Campbell, E. M.

AU - Ryan, R. M.

AU - Yool, A. J.

N1 - MEDLINE® is the source for the MeSH terms of this document.

PY - 2011/10/15

Y1 - 2011/10/15

N2 - Glutamate transport is coupled to the co-transport of 3 Na+ and 1 H+ followed by the counter-transport of 1 K+. In addition, glutamate and Na+ binding to glutamate transporters generates an uncoupled anion conductance. The human glial glutamate transporter EAAT1 (excitatory amino acid transporter 1) also allows significant passive and active water transport, which suggests that water permeation through glutamate transporters may play an important role in glial cell homoeostasis. Urea also permeates EAAT1 and has been used to characterize the permeation properties of the transporter. We have previously identified a series of mutations that differentially affect either the glutamate transport process or the substrate-activated channel function of EAAT1. The water and urea permeation properties of wild-type EAAT1 and two mutant transporters were measured to identify which permeation pathway facilitates the movement of these molecules. We demonstrate that there is a significant rate of L-glutamate-stimulated passive and active water transport. Both the passive and active L-glutamate-stimulated water transport is most closely associated with the glutamate transport process. In contrast, L-glutamate-stimulated [14C]urea permeation is associated with the anion channel of the transporter. However, there is also likely to be a transporter-specific, but glutamate independent, flux of water via the anion channel.

AB - Glutamate transport is coupled to the co-transport of 3 Na+ and 1 H+ followed by the counter-transport of 1 K+. In addition, glutamate and Na+ binding to glutamate transporters generates an uncoupled anion conductance. The human glial glutamate transporter EAAT1 (excitatory amino acid transporter 1) also allows significant passive and active water transport, which suggests that water permeation through glutamate transporters may play an important role in glial cell homoeostasis. Urea also permeates EAAT1 and has been used to characterize the permeation properties of the transporter. We have previously identified a series of mutations that differentially affect either the glutamate transport process or the substrate-activated channel function of EAAT1. The water and urea permeation properties of wild-type EAAT1 and two mutant transporters were measured to identify which permeation pathway facilitates the movement of these molecules. We demonstrate that there is a significant rate of L-glutamate-stimulated passive and active water transport. Both the passive and active L-glutamate-stimulated water transport is most closely associated with the glutamate transport process. In contrast, L-glutamate-stimulated [14C]urea permeation is associated with the anion channel of the transporter. However, there is also likely to be a transporter-specific, but glutamate independent, flux of water via the anion channel.

KW - anion channel

KW - glutamate transport

KW - urea

KW - water transport

UR - http://www.scopus.com/inward/record.url?scp=80053280649&partnerID=8YFLogxK

U2 - 10.1042/BJ20110905

DO - 10.1042/BJ20110905

M3 - Article

AN - SCOPUS:80053280649

VL - 439

SP - 333

EP - 340

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 2

ER -