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J Neurosci
2005 Feb 16;257:1730-6. doi: 10.1523/JNEUROSCI.4138-04.2005.
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Small-scale molecular motions accomplish glutamate uptake in human glutamate transporters.
Koch HP
,
Larsson HP
.
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Glutamate transporters remove glutamate from the synaptic cleft to maintain efficient synaptic communication between neurons and to prevent glutamate concentrations from reaching neurotoxic levels. Glutamate transporters play an important role in ischemic neuronal death during stroke and have been implicated in epilepsy and amytropic lateral sclerosis. However, the molecular structure and the glutamate-uptake mechanism of these transporters are not well understood. The most recent models of glutamate transporters have three or five subunits, each with eight transmembrane domains, and one or two membrane-inserted loops. Here, using fluorescence resonance energy transfer (FRET) analysis, we have determined the relative position of the extracellular regions of these domains. Our results are consistent with a trimeric glutamate transporter with a large (>45 A) extracellular vestibule. In contrast to other transport proteins, our FRET measurements indicate that there are no large-scale motions in glutamate transporters and that glutamate uptake is accompanied by relatively small motions around the glutamate-binding sites. The large extracellular vestibule and the small-scale conformational changes could contribute to the fast kinetics predicted for glutamate transporters. Furthermore, we show that, despite the multimeric nature of glutamate transporters, the subunits function independently.
Abramson,
Structure and mechanism of the lactose permease of Escherichia coli.
2003, Pubmed
Abramson,
Structure and mechanism of the lactose permease of Escherichia coli.
2003,
Pubmed
Arriza,
Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.
1994,
Pubmed
,
Xenbase
Arriza,
Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance.
1997,
Pubmed
,
Xenbase
Bergles,
Clearance of glutamate inside the synapse and beyond.
1999,
Pubmed
Cao,
Amino acid residues that control pH modulation of transport-associated current in mammalian serotonin transporters.
1998,
Pubmed
,
Xenbase
Chaudhry,
Glutamate transporters in glial plasma membranes: highly differentiated localizations revealed by quantitative ultrastructural immunocytochemistry.
1995,
Pubmed
Danbolt,
Glutamate uptake.
2001,
Pubmed
DeFelice,
Transporter structure and mechanism.
2004,
Pubmed
Dehnes,
The glutamate transporter EAAT4 in rat cerebellar Purkinje cells: a glutamate-gated chloride channel concentrated near the synapse in parts of the dendritic membrane facing astroglia.
1998,
Pubmed
Eskandari,
Pentameric assembly of a neuronal glutamate transporter.
2000,
Pubmed
,
Xenbase
Fairman,
An excitatory amino-acid transporter with properties of a ligand-gated chloride channel.
1995,
Pubmed
,
Xenbase
Gendreau,
A trimeric quaternary structure is conserved in bacterial and human glutamate transporters.
2004,
Pubmed
,
Xenbase
Grunewald,
The accessibility of a novel reentrant loop of the glutamate transporter GLT-1 is restricted by its substrate.
2000,
Pubmed
Grunewald,
Conformational changes monitored on the glutamate transporter GLT-1 indicate the existence of two neurotransmitter-bound states.
1995,
Pubmed
Grunewald,
Biotinylation of single cysteine mutants of the glutamate transporter GLT-1 from rat brain reveals its unusual topology.
1998,
Pubmed
Haugeto,
Brain glutamate transporter proteins form homomultimers.
1996,
Pubmed
Huang,
Structure and mechanism of the glycerol-3-phosphate transporter from Escherichia coli.
2003,
Pubmed
Jardetzky,
Simple allosteric model for membrane pumps.
1966,
Pubmed
Kanai,
Primary structure and functional characterization of a high-affinity glutamate transporter.
1992,
Pubmed
,
Xenbase
Kanai,
The neuronal and epithelial human high affinity glutamate transporter. Insights into structure and mechanism of transport.
1994,
Pubmed
,
Xenbase
Kanner,
The dual-function glutamate transporters: structure and molecular characterisation of the substrate-binding sites.
2002,
Pubmed
Kühlbrandt,
Structure, mechanism, and regulation of the Neurospora plasma membrane H+-ATPase.
2002,
Pubmed
Larsson,
Fluorometric measurements of conformational changes in glutamate transporters.
2004,
Pubmed
,
Xenbase
Lester,
Permeation properties of neurotransmitter transporters.
1994,
Pubmed
Lester,
Listening to neurotransmitter transporters.
1996,
Pubmed
Levy,
Stoichiometry of the glial glutamate transporter GLT-1 expressed inducibly in a Chinese hamster ovary cell line selected for low endogenous Na+-dependent glutamate uptake.
1998,
Pubmed
Lin,
Molecular cloning and expression of the rat EAAT4 glutamate transporter subtype.
1998,
Pubmed
,
Xenbase
Läuger,
A channel mechanism for electrogenic ion pumps.
1979,
Pubmed
Otis,
Anion currents and predicted glutamate flux through a neuronal glutamate transporter.
1998,
Pubmed
Pines,
Cloning and expression of a rat brain L-glutamate transporter.
1992,
Pubmed
Rothstein,
Localization of neuronal and glial glutamate transporters.
1994,
Pubmed
Seal,
A model for the topology of excitatory amino acid transporters determined by the extracellular accessibility of substituted cysteines.
2000,
Pubmed
Seal,
Identification and characterization of a cDNA encoding a neuronal glutamate transporter from Drosophila melanogaster.
1998,
Pubmed
,
Xenbase
Seal,
A reentrant loop domain in the glutamate carrier EAAT1 participates in substrate binding and translocation.
1998,
Pubmed
Selvin,
Fluorescence resonance energy transfer.
1995,
Pubmed
Slotboom,
A conserved serine-rich stretch in the glutamate transporter family forms a substrate-sensitive reentrant loop.
1999,
Pubmed
Slotboom,
Cysteine-scanning mutagenesis reveals a highly amphipathic, pore-lining membrane-spanning helix in the glutamate transporter GltT.
2001,
Pubmed
Slotboom,
Membrane topology of the C-terminal half of the neuronal, glial, and bacterial glutamate transporter family.
1996,
Pubmed
Storck,
Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain.
1992,
Pubmed
,
Xenbase
Tanaka,
Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1.
1997,
Pubmed
Toyoshima,
Structural changes in the calcium pump accompanying the dissociation of calcium.
2002,
Pubmed
Toyoshima,
Structural basis of ion pumping by Ca2+-ATPase of the sarcoplasmic reticulum.
2004,
Pubmed
Toyoshima,
Crystal structure of the calcium pump with a bound ATP analogue.
2004,
Pubmed
Vidaver,
Inhibition of parallel flux and augmentation of counter flux shown by transport models not involving a mobile carrier.
1966,
Pubmed
Watanabe,
Amygdala-kindled and pentylenetetrazole-induced seizures in glutamate transporter GLAST-deficient mice.
1999,
Pubmed
Yernool,
Trimeric subunit stoichiometry of the glutamate transporters from Bacillus caldotenax and Bacillus stearothermophilus.
2003,
Pubmed
Yernool,
Structure of a glutamate transporter homologue from Pyrococcus horikoshii.
2004,
Pubmed
Zarbiv,
Cysteine scanning of the surroundings of an alkali-ion binding site of the glutamate transporter GLT-1 reveals a conformationally sensitive residue.
1998,
Pubmed
Zerangue,
Flux coupling in a neuronal glutamate transporter.
1996,
Pubmed
,
Xenbase
