Alternate splicing and expression of the glutamate transporter EAAT5 in the rat retina

Lee, Aven; Anderson, Ashley; Barnett, Nigel L.; Stevens, Melissa G.; Pow, David V.

doi:10.1016/j.gene.2012.07.010

Cited by 18 publications

(15 citation statements)

References 25 publications

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“…More recently, multiple splice variants of EAAT5 have been reported and it is predicted that some of those EAAT5 isoforms possess one of the above functions while some possess the other (Lee, Anderson et al 2012). There are multiple subtypes of DBC C and DBC R as classified by their morphology and photoreceptor input (Ghosh, Bujan et al 2004; Pang, Gao et al 2010) in mouse.…”

Section: Discussionmentioning

confidence: 99%

Possible roles of glutamate transporter EAAT5 in mouse cone depolarizing bipolar cell light responses

Tse

Chung

2014

Vision Research

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A remarkable feature of neuronal glutamate transporters (EAATs) is their dual functions of classical carriers and ligand-gated chloride (CI−) channels. CI− conductance is rapidly activated by glutamate in subtype EAAT5, which mediates light responses in depolarizing bipolar cells (DBC) in retinae of lower vertebrates. In this study, we examine whether EAAT5 also mediates the DBC light response in mouse. We took advantage of an infrared illuminated micro-injection system, and studied the effects of the EAAT blocker (TBOA) and a glutamate receptor agonist (LAP4) on the mouse electroretinogram (ERG) b-wave responses. Our results showed that TBOA and LAP4 shared similar temporal patterns of inhibition: both inhibited the ERG b-wave shortly after injection and recovered with similar time courses. TBOA inhibited the b-wave completely at mesopic light intensity with an IC50 value about 1 log unit higher than that of LAP4. The inhibitory effects of TBOA and LAP4 were found to be additive in the photopic range. Furthermore, TBOA alone inhibited the b-wave in the cone operative range in knockout mice lacking DBCRs at a low concentration that did not alter synaptic glutamate clearance activity. It also produced a stronger inhibition than that of LAP4 on the cone-driven b-wave measured with a double flash method in wildtype mice. These electrophysiological data suggest a significant role for EAAT5 in mediating cone-driven DBC light responses. Our immunohistochemistry data indicated the presence of postsynaptic EAAT5 on some DBCCs and some DBCRs, providing an anatomical basis for EAAT5’s role in DBC light responses.

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Section: Discussionmentioning

confidence: 99%

Possible roles of glutamate transporter EAAT5 in mouse cone depolarizing bipolar cell light responses

Tse

Chung

2014

Vision Research

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“…We have recently shown that the EAAT5 gene in rodents is subject to alternate splicing and have demonstrated by PCR cloning and sequencing the presence of five novel splice variant forms of EAAT5 which skip either parts of exons or complete exons in the rat retina. Furthermore, we showed that each of these splice variants is expressed at the protein level as assessed by Western blotting using splice-specific antibodies that we have generated (Lee et al, 2012a). However, in this study we re-evaluated these findings with respect to the human retina, since any variant form is of far greater interest to biomedical researchers if it is actually expressed and functional in humans.…”

Section: Introductionmentioning

confidence: 95%

“…Polyclonal EAAT5 antisera against hEAAT5v was generated by immunizing rabbits according to standard protocols (Pow et al, 1993;Pow at al., 2003;Rauen et al, 2004) which we have successfully used to identify splice variants of other EAATs (Lee at al., 2012a(Lee at al., , 2012b. The sequence used was KNQVRALQCPRSLPPA and represents a novel…”

Section: Antibodiesmentioning

confidence: 99%

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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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“…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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Alternate splicing and expression of the glutamate transporter EAAT5 in the rat retina

Cited by 18 publications

References 25 publications

Possible roles of glutamate transporter EAAT5 in mouse cone depolarizing bipolar cell light responses

Possible roles of glutamate transporter EAAT5 in mouse cone depolarizing bipolar cell light responses

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

Neuronal vs glial glutamate uptake: Resolving the conundrum

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