Functional Properties of the Retinal Glutamate Transporters GLT-1c and EAAT5

Schneider, Nicole; Cordeiro, Soenke; Machtens, Jan‐Philipp; Braams, Simona; Rauen, Thomas; Fahlke, Christoph

doi:10.1074/jbc.m113.517177

Cited by 56 publications

(62 citation statements)

References 44 publications

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“…10 increases in D-aspartate uptake for both hEAAT5 and hEAAT5v are consistent with data from recent studies showing that EAAT5 is a slow, low capacity glutamate transporter (Gameiro et al, 2011;Schneider et al 2014). The apparant K m value for D-aspartate was ~54 µM (Fig 3B), which is in agreement with the previously reported value for hEAAT5 (Arriza et al, 1997).…”

Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 92%

A novel splice variant of the Excitatory Amino Acid Transporter 5: Cloning, immunolocalization and functional characterization of hEAAT5v in human retina

Lee

Stevens

Anderson

et al. 2016

Neurochemistry International

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. have performed immunocytochemistry to demonstrate expression in photoreceptors in human retina. We noted that in retinas afflicted by dry aged-related macular degeneration (AMD), there was a loss of hEAAT5v from the lesioned area and from photoreceptors adjacent to the lesion. We conclude that hEAAT5v protein expression may be perturbed in peri-lesional areas of AMD-afflicted retinas that do not otherwise exhibit evidence of damage. The loss of hEAAT5v could, therefore, represent an early pathological change in the development of AMD and might be involved in its aetiology.

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Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 92%

A novel splice variant of the Excitatory Amino Acid Transporter 5: Cloning, immunolocalization and functional characterization of hEAAT5v in human retina

Lee

Stevens

Anderson

et al. 2016

Neurochemistry International

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“…In transporters with a normal substrate-gated anion conductance, application of saturating concentrations of glutamate would be expected to result in a 2-3-fold increase in the current amplitude. This has been consistently observed for EAAT2 (6), EAAT3 (37), EAAT4 (6,9,30), and EAAT5 (38). As predicted, oocytes expressing EAAT1 WT displayed current amplitudes in the presence of 1 mM glutamate that were 3-fold larger than in its absence (Fig.…”

Section: -I)supporting

confidence: 84%

“…4B and Table 1), together with the inability of substrate to further activate the anion conductance, strongly suggest that the anion channel exists in a constitutively open state. The activation of EAATassociated anion channels has also been observed to be voltagedependent (6,(37)(38)(39)(40). In oocytes expressing EAAT1 WT, we observed a voltage-dependent relative open probability with a V 50 of Ϫ25.6 Ϯ 1.2 mV (Fig.…”

Section: Discussionmentioning

confidence: 52%

A Mutation in Transmembrane Domain 7 (TM7) of Excitatory Amino Acid Transporters Disrupts the Substrate-dependent Gating of the Intrinsic Anion Conductance and Drives the Channel into a Constitutively Open State

Torres-Salazar

Jiang

Divito

et al. 2015

Journal of Biological Chemistry

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Background:The anion channel gating mechanism in glutamate transporters remains undefined. Results: An EAAT1 mutant, R388D/E, displays reduced transport and exists preferentially in a substrate-independent open channel state. Conclusion: Arg-388 is essential for the structural transitions that drive the equilibrium between channel and transport modes. Significance: The data presented indicate that transport and anion conducting states may be mediated by closely linked alternative conformations.

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“…EAAT4 has the highest affinity with reported Km values in the range 0. 6-3.3 µM (Fairman et al, 1995;Lin et al, 1998;#19512};Mim et al, 2005), while EAAT5 has the lowest affinity with Km values in the range 61-63 µM (Gameiro et al, 2011;Schneider et al, 2014).…”

Section: Identification Of Plasma Membrane Glutamate Transportersmentioning

confidence: 99%

“…EAAT5 (Arriza et al, 1997) is present in the retina at significant levels (Eliasof et al, 1998;Veruki et al, 2006;Schneider et al, 2014), and it may be subject to variable splicing (Lee et al, 2012), but has not been reported in other parts of the central nervous system. It is present in vestibular hair cells (Dalet et al, 2012), in the heart (Arriza et al, 1997;Martinov et al, 2014), in skeletal muscle (Arriza et al, 1997) and possibly at low levels in several other peripheral organs (Lee et al, 2013).…”

Section: Eaat4mentioning

confidence: 99%

Neuronal vs glial glutamate uptake: Resolving the conundrum

Danbolt

Furness

Zhou

2016

Neurochemistry International

180

152

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Neither normal brain function nor the pathological processes involved in neurological diseases can be adequately understood without knowledge of the release, uptake and metabolism of glutamate. The reason for this is that glutamate (a) is the most abundant amino acid in the brain, (b) is at the cross-roads between several metabolic pathways, and (c) serves as the major excitatory neurotransmitter. In fact most brain cells express glutamate receptors and are thereby influenced by extracellular glutamate. In agreement, brain cells have powerful uptake systems that constantly remove glutamate from the extracellular fluid and thereby limit receptor activation. It has been clear since the 1970s that both astrocytes and neurons express glutamate transporters. However, the relative contribution of neuronal and glial transporters to the total glutamate uptake activity, however, as well as their functional importance, has been hotly debated ever since. The present short review provides (a) an overview of what we know about neuronal glutamate uptake as well as an historical description of how we got there, and (b) a hypothesis reconciling apparently contradicting observations thereby possibly resolving the paradox. ABBREVIATIONSCre, Cyclization recombinase (Le and Sauer, 2000); EAAC1, glutamate transporter (EAAT3; slc1a1; Kanai and Hediger, 1992; Bjørås et al., 1996); EAAT, excitatory amino acid transporter (synonym to glutamate transporter); GABA, γ-aminobutyric acid; GLAST, rat glutamate transporter (EAAT1; slc1a3; Storck et al., 1992;Tanaka, 1993a); GLT-1, rat glutamate transporter (EAAT2; slc1a2; Pines et al., 1992); GLUL, glutamine synthetase; TBOA, DL-threo-β-benzyloxyaspartate AbstractNeither normal brain function nor the pathological processes involved in neurological diseases can be adequately understood without knowledge of the release, uptake and metabolism of glutamate. The reason for this is that glutamate (a) is the most abundant amino acid in the brain, (b) is at the cross-roads between several metabolic pathways, and (c) serves as the major excitatory neurotransmitter. In fact most brain cells express glutamate receptors and are thereby influenced by extracellular glutamate. In agreement, brain cells have powerful uptake systems that constantly remove glutamate from the extracellular fluid and thereby limit receptor activation. It has been clear since the 1970s that astrocytes and neurons express glutamate transporters. The relative contribution of neuronal and glial transporters to the total glutamate uptake activity, however, as well as their functional importance, has been hotly debated ever since. The present short review provides (a) an overview of what we know about neuronal glutamate uptake as well as an historical description of how we got there, and (b) an hypothesis reconciling apparently contradicting observations thereby possibly resolving the paradox.

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Functional Properties of the Retinal Glutamate Transporters GLT-1c and EAAT5

Abstract: Background: GLT-1c and EAAT5 are two excitatory amino acid transporters co-expressed in retinal neurons. Results: GLT-1c and EAAT5 differ in glutamate and Na ϩ affinity, individual transport rates as well as in unitary anion current

Cited by 56 publications

References 44 publications

A novel splice variant of the Excitatory Amino Acid Transporter 5: Cloning, immunolocalization and functional characterization of hEAAT5v in human retina

A novel splice variant of the Excitatory Amino Acid Transporter 5: Cloning, immunolocalization and functional characterization of hEAAT5v in human retina

A Mutation in Transmembrane Domain 7 (TM7) of Excitatory Amino Acid Transporters Disrupts the Substrate-dependent Gating of the Intrinsic Anion Conductance and Drives the Channel into a Constitutively Open State

Neuronal vs glial glutamate uptake: Resolving the conundrum

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