scholarly journals Interactions of alkali cations with glutamate transporters

2008 ◽  
Vol 364 (1514) ◽  
pp. 155-161 ◽  
Author(s):  
David C Holley ◽  
Michael P Kavanaugh
Keyword(s):  
Binding Sites ◽  
Chloride Channels ◽  
Glutamate Transporter ◽  
Structural Data ◽  
Glutamate Transporters ◽  
Cation Binding ◽  
Alkali Cations ◽  
Glutamate Binding ◽  
Plausible Mechanism ◽  
Exchange Behaviour

The transport of glutamate is coupled to the co-transport of three Na + ions and the countertransport of one K + ion. In addition to this carrier-type exchange behaviour, glutamate transporters also behave as chloride channels. The chloride channel activity is strongly influenced by the cations that are involved in coupled flux, making glutamate transporters representative of the ambiguous interface between carriers and channels. In this paper, we review the interaction of alkali cations with glutamate transporters in terms of these diverse functions. We also present a model derived from electrostatic mapping of the predicted cation-binding sites in the X-ray crystal structure of the Pyrococcus horikoshii transporter Glt Ph and in its human glutamate transporter homologue EAAT3. Two predicted Na + -binding sites were found to overlap precisely with the Tl + densities observed in the aspartate-bound complex. A novel third site predicted to favourably bind Na + (but not Tl + ) is formed by interaction with the substrate and the occluding HP2 loop. A fourth predicted site in the apo state exhibits selectivity for K + over both Na + and Tl + . Notably, this K + site partially overlaps the glutamate-binding site, and their binding is mutually exclusive. These results are consistent with kinetic and structural data and suggest a plausible mechanism for the flux coupling of glutamate with Na + and K + ions.

scholarly journals Vesicular Glutamate Transporters Use Flexible Anion and Cation Binding Sites for Efficient Accumulation of Neurotransmitter

Neuron ◽  
2014 ◽  
Vol 84 (6) ◽  
pp. 1287-1301 ◽  
Author(s):  
Julia Preobraschenski ◽  
Johannes-Friedrich Zander ◽  
Toshiharu Suzuki ◽  
Gudrun Ahnert-Hilger ◽  
Reinhard Jahn
Keyword(s):  
Binding Sites ◽  
Glutamate Transporters ◽  
Cation Binding ◽  
Vesicular Glutamate Transporters

scholarly journals Distinct roles of the Na+ binding sites in the allosteric coupling mechanism of the glutamate transporter homolog, GltPh.

2021 ◽  
Author(s):  
Francis Valiyaveetil ◽  
Erika Riederer ◽  
Pierre Moenne-Loccoz
Keyword(s):  
Binding Sites ◽  
Transport Mechanism ◽  
Glutamate Transporter ◽  
Glutamate Transporters ◽  
Coupling Mechanism ◽  
Conformational Switch ◽  
Allosteric Coupling ◽  
Partial Opening ◽  
Na Ions ◽  
The Individual

Glutamate transporters carry out the concentrative uptake of glutamate by harnessing the ionic gradients present across cellular membranes. A central step in the transport mechanism is the coupled binding of Na+ and substrate. The sodium coupled Asp transporter, GltPh is an archaeal homolog of glutamate transporters that has been extensively used to probe the transport mechanism. Previous studies have shown that hairpin-2 (HP2) functions as the extracellular gate for the aspartate binding site and plays a key role in the coupled binding of sodium and aspartate to GltPh. The binding sites for three Na+ ions (Na1-3) have been identified in GltPh but the specific roles of the individual Na+ sites in the binding process has not been elucidated. In this study, we developed assays to probe Na+ binding to the Na1 and Na3 sites and to monitor the conformational switch in the NMDGT motif. We used these assays along with a fluorescence assay to monitor HP2 movement and EPR spectroscopy to show that Na+ binding to the Na3 site is required for the NMDGT conformational switch while Na+ binding to the Na1 site is responsible for the partial opening of HP2. Complete opening of HP2 requires the conformational switch of the NMDGT motif and therefore Na+ binding to both the Na1 and the Na3 sites. Based on our studies we also propose an alternate pathway for the coupled binding of Na+ and Asp.

Adrenal [3H]glutamate binding sites

1988 ◽  
Vol 7 ◽  
pp. S157
Author(s):  
Yukio Yoneda ◽  
Kiyokazu Ogita
Keyword(s):  
Binding Sites ◽  
Glutamate Binding

scholarly journals First Characterization of an Archaeal GTP-Dependent Phosphoenolpyruvate Carboxykinase from the Hyperthermophilic Archaeon Thermococcus kodakaraensis KOD1

2004 ◽  
Vol 186 (14) ◽  
pp. 4620-4627 ◽  
Author(s):  
Wakao Fukuda ◽  
Toshiaki Fukui ◽  
Haruyuki Atomi ◽  
Tadayuki Imanaka
Keyword(s):  
Binding Sites ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Cation Binding ◽  
Activity Levels ◽  
Binding Region ◽  
Hyperthermophilic Archaeon ◽  
Dependent Activity ◽  
Additional Role

ABSTRACT Phosphoenolpyruvate carboxykinase (PCK), which catalyzes the nucleotide-dependent, reversible decarboxylation of oxaloacetate to yield phosphoenolpyruvate and CO2, is one of the important enzymes in the interconversion between C3 and C4 metabolites. This study focused on the first characterization of the enzymatic properties and expression profile of an archaeal PCK from the hyperthermophilic archaeon Thermococcus kodakaraensis (Pck Tk ). Pck Tk showed 30 to 35% identities to GTP-dependent PCKs from mammals and bacteria but was located in a branch distinct from that of the classical enzymes in the phylogenetic tree, together with other archaeal homologs from Pyrococcus and Sulfolobus spp. Several catalytically important regions and residues, found in all known PCKs irrespective of their nucleotide specificities, were conserved in Pck Tk . However, the predicted GTP-binding region was unique compared to those in other GTP-dependent PCKs. The recombinant Pck Tk actually exhibited GTP-dependent activity and was suggested to possess dual cation-binding sites specific for Mn2+ and Mg2+. The enzyme preferred phosphoenolpyruvate formation from oxaloacetate, since the Km value for oxaloacetate was much lower than that for phosphoenolpyruvate. The transcription and activity levels in T. kodakaraensis were higher under gluconeogenic conditions than under glycolytic conditions. These results agreed with the role of Pck Tk in providing phosphoenolpyruvate from oxaloacetate as the first step of gluconeogenesis in this hyperthermophilic archaeon. Additionally, under gluconeogenic conditions, we observed higher expression levels of Pck Tk on pyruvate than on amino acids, implying that it plays an additional role in the recycling of excess phosphoenolpyruvate produced from pyruvate, replacing the function of the anaplerotic phosphoenolpyruvate carboxylase that is missing from this archaeon.

Identification of glutamate-binding sites in Caenorhabditis elegans

1990 ◽  
Vol 36 (3) ◽  
pp. 220-228 ◽  
Author(s):  
James M. Schaeffer ◽  
Teresa White ◽  
Alan R. Bergstrom ◽  
Kenneth E. Wilson ◽  
Mervyn J. Turner
Keyword(s):  
Caenorhabditis Elegans ◽  
Binding Sites ◽  
Glutamate Binding

Development of glutamate binding sites and their regulation by calcium in rat hippocampus

1981 ◽  
Vol 1 (1) ◽  
pp. 37-48 ◽  
Author(s):  
Michel Baudry ◽  
Denise Arst ◽  
Michael Oliver ◽  
Gary Lynch
Keyword(s):  
Binding Sites ◽  
Rat Hippocampus ◽  
Glutamate Binding

Continuous versus intermittent theta burst stimulation in the treatment of experimental autoimmune encephalomyelitis: a glutamate transporters study

2020 ◽  
Author(s):  
Milica Ninkovic ◽  
Mirjana Djukic ◽  
Bojana Mancic ◽  
Petar Milosavljevic ◽  
Ivana Stojanovic ◽  
...  
Keyword(s):  
Glutamate Transporter ◽  
Glutamate Transporters ◽  
Dark Agouti ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Autoimmune Encephalomyelitis ◽  
Glial Glutamate Transporter ◽  
Elevated Expression ◽  
Underlying Mechanisms ◽  
Theta Burst

Abstract Background: Synaptic overload with glutamate aggravates neurotransmission and worsen the progression of the neurodegenerative disease, such as multiple sclerosis (MS). The experimentally induced autoimmune encephalomyelitis (EAE) in rats is a well-established animal model to study MS. Glutamate reuptake occurs by glial glutamate transporter (GLT-1), and glutamate-aspartate transporter (GLAST) localized predominantly in astrocytes terminals. The focus of the study addressing the expression of these transporters in EAE rats and those subjected to theta burst stimulation (TBS), that promotes long-lasting modulation of neuronal activity in rats/humans. Leading by the reported outcomes of TBS, we examined if TBS underlying mechanisms refer to astroglial glutamate transporters status.Methods : We studied changes in the expression of glial glutamate transporter GLT-1 and glutamate-aspartate transporter (GLAST), and glial fibrillary acidic protein (GFAP), in the spinal cord of EAE rats, subjected to intermittent (iTBS) and continuous (cTBS) theta burst stimulation. We quantified the expression of GLAST, GLT-1, and GFAP by immunofluorescence in control and experimental groups of Dark Agouti rats.Results: EAE elevated expression of GFAP, GLAST, and GLT-1. Both TBSs reduced the expression of GFAP. Continual TBS did not interfere with glutamate transporters in EAE rats, while iTBS decreased GLT-1, and increased GLAST.Conclusion: Continual TBS reduced astrogliosis more efficiently than iTBS, in EAE rats. Besides, it did not mitigate the glutamate transporters' expression; thus, glutamate reuptake remained upraised in cTBS exposed EAE rats. Accordingly, we concluded that cTBS might advance the remyelination of damaged neuronal cells in EAE rats. The future clinical trials on the treatment of MS may consider the data of this pre-clinical animal study.

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