Cloning and expression of a rat brain L-glutamate transporter

Pines, Gilia; Danbolt, Niels Christian; Bjørås, Magnar; Zhang, Yumin; Bendahan, Annie; Eide, Lars; Koepsell, Hermann; Storm‐Mathisen, Jon; Seeberg, Erling; Kanner, Baruch I.

doi:10.1038/360464a0

Cited by 1,180 publications

(784 citation statements)

References 31 publications

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“…4 A probe designed from the cloned sequence detected an 11 kb fragment on a northern blot in the brain but not in peripheral tissues. Remarkably, this was the first observation that the GLT1 transcript was much longer than the cloned sequence.…”

Section: Clarification Of Nomenclaturementioning

confidence: 99%

EAAT2 regulation and splicing: relevance to psychiatric and neurological disorders

Lauriat

McInnes

2007

Mol Psychiatry

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The excitatory amino acid transporter 2 (EAAT2) is responsible for the majority of glutamate uptake in the brain and its dysregulation has been associated with multiple psychiatric and neurological disorders. However, investigation of this molecule has been complicated by its complex pattern of alternative splicing, including three coding isoforms and multiple 5 0 -and 3 0 -UTRs that may have a regulatory function. It is likely that these sequences permit modulation of EAAT2 expression with spatial, temporal and or activity-dependent specificity; however, few studies have attempted to delineate the function of these sequences. Additionally, there are problems with the use of antibodies to study protein localization, possibly due to posttranslational modification of critical amino acid residues. This review describes what is currently known about the regulation of EAAT2 mRNA and protein isoforms and concludes with a summary of studies showing dysregulation of EAAT2 in psychiatric and neurological disorders. EAAT2 has been either primarily or secondarily implicated in a multitude of neuropsychiatric diseases in addition to the normal physiology of learning and memory. Thus, this molecule represents an intriguing therapeutic target once we improve our understanding of how it is regulated under normal conditions.

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Section: Clarification Of Nomenclaturementioning

confidence: 99%

EAAT2 regulation and splicing: relevance to psychiatric and neurological disorders

Lauriat

McInnes

2007

Mol Psychiatry

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“…Three different glutamate transporters were cloned from rat brain [42,52] and from rabbit intestine [28]. Their human counterparts have 95% homology in amino acid sequence and were respectively called EAAT1, EAAT2 and EAAT3 [2].…”

Section: Introductionmentioning

confidence: 99%

Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer’s disease

Zoia

Cogliati

Tagliabue

et al. 2004

Neurobiology of Aging

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Platelets release glutamate upon activation and are an important clearance system of the amino acid from blood, through high-affinity glutamate uptake, similar to that described in brain synaptosomes. Since platelet glutamate uptake is decreased in neurodegenerative disorders, we performed a morphological and molecular characterization of platelet glutamate transporters. The three major brain glutamate transporters EAAT1, EAAT2 and EAAT3 are expressed in platelets, with similar molecular weight, although at lower density than brain. A Na + -dependent-high-affinity glutamate uptake was competitively inhibited by known inhibitors but not by dihydrokainic acid, suggesting platelet EAAT2 does not play a major role in glutamate uptake at physiological conditions. We observed decreased glutamate uptake V max , without modification of transporter affinity, in aging, which could be linked to the selective decrease of EAAT1 expression and mRNA. Moreover, in AD patients we found a further EAAT1 reduction compared to age-matched controls, which could explain the decrease of platelet uptake previously described. Platelet glutamate transporters may be used as peripheral markers to investigate the role of glutamate in patients with neuropsychiatric disorders.

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“…Several isoforms of amino acid transporters, named EAAT1 (GLAST), EAAT2 (GLT-1), EAAT3 (EAAC1), EAAT4 and EAAT5, have been identified in the central and peripheral nervous systems of different species [3][4][5][6][7][8]. Their function relies on the Na + gradient across the plasma membrane and on the countertransport of K + and OH − [1].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of glutamate uptake by a polypeptide toxin (phoneutriatoxin 3-4) from the spider Phoneutria nigriventer

Reis

Prado

Kalapothakis

et al. 1999

Biochemical Journal

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Glutamate concentration increases significantly in the extracellular compartment during brain ischaemia and anoxia. This increase has an important Ca2+-independent component, which is due in part to the reversal of glutamate transporters of the plasma membrane of neurons and glia. The toxin phoneutriatoxin 3-4 (Tx3-4) from the spider Phoneutria nigriventer has been reported to decrease the evoked glutamate release from synaptosomes by inhibiting Ca2+ entry via voltage-dependent Ca2+ channels. However, we report here that Tx3-4 is also able to inhibit the uptake of glutamate by synaptosomes in a time-dependent manner and that this inhibition in turn leads to a decrease in the Ca2+-independent release of glutamate. No other polypeptide toxin so far described has this effect. Our results suggest that Tx3-4 can be a valuable tool in the investigation of function and dysfunction of glutamatergic neurotransmission in diseases such as ischaemia.

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Cloning and expression of a rat brain L-glutamate transporter

Cited by 1,180 publications

References 31 publications

EAAT2 regulation and splicing: relevance to psychiatric and neurological disorders

EAAT2 regulation and splicing: relevance to psychiatric and neurological disorders

Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer’s disease

Inhibition of glutamate uptake by a polypeptide toxin (phoneutriatoxin 3-4) from the spider Phoneutria nigriventer

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