Exon 4-skipping GLT-1: A new form of an abundantly expressed glutamate transporter

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

doi:10.1016/j.neulet.2011.09.029

Cited by 7 publications

(4 citation statements)

References 22 publications

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“…EAAT2 antibody labeled a 55 kDa band on Western blot, consistent with prior studies (Additional file 3 : Figure S2A) [ 23 , 24 ]. Several other studies have reported a slightly higher molecular weight (~60 kDa) for EAAT2, which might be due to differential splicing and/or glycosylation [ 24 , 26 , 27 ]. We also observed faint labeling of much higher molecular weight bands, suggesting that EAAT2 also forms multimers, as previously described (Additional file 3 : Figure S2A) [ 23 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

Decreased EAAT2 protein expression in the essential tremor cerebellar cortex

Lee

Cheng

Lin

et al. 2014

acta neuropathol commun

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Genetic polymorphisms in Solute carrier family 1 (glial high affinity glutamate transporter), member 2 (SLC1A2) have been linked with essential tremor. SLC1A2 encodes excitatory amino acid transporter type 2 (EAAT2), which clears glutamate from the synaptic cleft. One postulated mechanism for essential tremor is the over-excitation of glutamatergic olivo-cerebellar climbing fibers, leading to excitotoxic death of Purkinje cells. Other glutamatergic excitatory signals are transmitted to Purkinje cells via parallel fibers of cerebellar granule neurons. Therefore, the expression level of glutamate transporters could be important in essential tremor pathogenesis. Using Western blotting, we compared the expression levels of the two main glutamate transporters in the cerebellar cortex, EAAT1 and EAAT2, in postmortem tissue from 16 essential tremor cases and 13 age-matched controls. We also studied the localization of EAAT1 and EAAT2 using immunohistochemistry in 10 essential tremor cases and 12 controls. EAAT1 protein levels were similar in cases and controls (1.12 ± 0.83 vs. 1.01 ± 0.69, p =0.71) whereas EAAT2 protein levels in essential tremor cases were only 1/3 of that in controls (0.35 ± 0.23 vs. 1.00 ± 0.62, p < 0.01). Interestingly, EAAT2, but not EAAT1, was expressed in astrocytic processes surrounding the Purkinje cell axon initial segment, a region of previously observed pathological changes in essential tremor. Our main finding, a significant reduction in cerebellar cortical EAAT2 protein levels in essential tremor, suggests that Purkinje cells in essential tremor might be more vulnerable to excitotoxic damage than those of controls.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-014-0157-z) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Decreased EAAT2 protein expression in the essential tremor cerebellar cortex

Lee

Cheng

Lin

et al. 2014

acta neuropathol commun

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“…Alternative EAAT N-termini and C-termini have been identified, resulting from exon skipping splice variants and alternately spliced 5' untranslated regions and 3' regions. 28 – 30 The exon skipping forms include EAAT2 exon7skipping, 31 EAAT2 exon8skipping, 32 , 33 EAAT2 exon9skipping, 34 EAAT2 exon4skipping, 35 EAAT2 exon7exon9skipping, 36 and EAAT2 intron7retaining, 37 which have all been detected in brain tissue. EAAT1 exon9skipping variant, an EAAT1 splice variant which lacks the region homologous to EAAT2 exon9skipping, has also been described.…”

Section: Basic Biology Of Glutamate Transportersmentioning

confidence: 99%

The role of glutamate transporters in the pathophysiology of neuropsychiatric disorders

2017

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Altered glutamate transporter expression is a common feature of many neuropsychiatric conditions, including schizophrenia. Excitatory amino acid transporters (EAATs) are responsible for the reuptake of glutamate, preventing non-physiological spillover from the synapse. Postmortem studies have revealed significant dysregulation of EAAT expression in various brain regions at the cellular and subcellular level. Recent animal studies have also demonstrated a role for glutamate spillover as a mechanism of disease. In this review, we describe current evidence for the role of glutamate transporters in regulating synaptic plasticity and transmission. In neuropsychiatric conditions, EAAT splice variant expression is altered. There are changes in the localization of the transporters and disruption of the metabolic and structural protein network that supports EAAT activity. This results in aberrant neuroplasticity and excitatory signaling, contributing to the symptoms associated with neuropsychiatric disease. Understanding the complex functions of glutamate transporters will clarify the relevance of their role in the pathophysiology of neuropsychiatric disorders.

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“…The full length GLT-1 (often referred to as GLT-1a) has an approximate molecular weight, following glycosylation, of about 62 kDa [52]. Together with the original form, several post-transcriptionally regulated isoforms with different molecular weight have been described, including alternative splicing producing different N- and C-termini [53]–[55] and exon-skipping splice variants [56]–[58].…”

Section: Discussionmentioning

confidence: 99%

Impairment of Neuronal Glutamate Uptake and Modulation of the Glutamate Transporter GLT-1 Induced by Retinal Ischemia

et al. 2013

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Excitotoxicity has been implicated in the retinal neuronal loss in several ocular pathologies including glaucoma. Dysfunction of Excitatory Amino Acid Transporters is often a key component of the cascade leading to excitotoxic cell death. In the retina, glutamate transport is mainly operated by the glial glutamate transporter GLAST and the neuronal transporter GLT-1. In this study we evaluated the expression of GLAST and GLT-1 in a rat model of acute glaucoma based on the transient increase of intraocular pressure (IOP) and characterized by high glutamate levels during the reperfusion that follows the ischemic event associated with raised IOP. No changes were reported in GLAST expression while, at neuronal level, a reduction of glutamate uptake and of transporter reversal-mediated glutamate release was observed in isolated retinal synaptosomes. This was accompanied by modulation of GLT-1 expression leading to the reduction of the canonical 65 kDa form and upregulation of a GLT-1-related 38 kDa protein. These results support a role for neuronal transporters in glutamate accumulation observed in the retina following an ischemic event and suggest the presence of a GLT-1 neuronal new alternative splice variant, induced in response to the detrimental stimulus.

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Exon 4-skipping GLT-1: A new form of an abundantly expressed glutamate transporter

Cited by 7 publications

References 22 publications

Decreased EAAT2 protein expression in the essential tremor cerebellar cortex

Decreased EAAT2 protein expression in the essential tremor cerebellar cortex

The role of glutamate transporters in the pathophysiology of neuropsychiatric disorders

Impairment of Neuronal Glutamate Uptake and Modulation of the Glutamate Transporter GLT-1 Induced by Retinal Ischemia

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