Uptake of Glutamate into Synaptic Vesicles by an Inorganic Phosphate Transporter

Bellocchio, Elizabeth E.; Reimer, Richard J.; Fremeau, Robert T.; Edwards, Robert H.

doi:10.1126/science.289.5481.957

Cited by 731 publications

(682 citation statements)

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“…The glutamatergic synapses of the cerebellar cortex were recognized on the basis of the topographic distribution in the cerebellar cortex layers and expression of vesicular glutamate transporters, vGluT-1 and/or vGluT-2 [39,40,58-62]. In the present study, we observed that the glutamatergic synapses between the parallel fibre terminals and the dendritic tree of Purkinje neurons frequently display co-localization of vGluT-1 with the three SNARE proteins examined.…”

Section: Discussionmentioning

confidence: 50%

VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

et al. 2011

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BackgroundThe aim of this study was to assess the distribution of key SNARE proteins in glutamatergic and GABAergic synapses of the adult rat cerebellar cortex using light microscopy immunohistochemical techniques. Analysis was made of co-localizations of vGluT-1 and vGluT-2, vesicular transporters of glutamate and markers of glutamatergic synapses, or GAD, the GABA synthetic enzyme and marker of GABAergic synapses, with VAMP-2, SNAP-25A/B and syntaxin-1.ResultsThe examined SNARE proteins were found to be diffusely expressed in glutamatergic synapses, whereas they were rarely observed in GABAergic synapses. However, among glutamatergic synapses, subpopulations which did not contain VAMP-2, SNAP-25A/B and syntaxin-1 were detected. They included virtually all the synapses established by terminals of climbing fibres (immunoreactive for vGluT-2) and some synapses established by terminals of parallel and mossy fibres (immunoreactive for vGluT-1, and for vGluT-1 and 2, respectively). The only GABA synapses expressing the SNARE proteins studied were the synapses established by axon terminals of basket neurons.ConclusionThe present study supplies a detailed morphological description of VAMP-2, SNAP-25A/B and syntaxin-1 in the different types of glutamatergic and GABAergic synapses of the rat cerebellar cortex. The examined SNARE proteins characterize most of glutamatergic synapses and only one type of GABAergic synapses. In the subpopulations of glutamatergic and GABAergic synapses lacking the SNARE protein isoforms examined, alternative mechanisms for regulating trafficking of synaptic vesicles may be hypothesized, possibly mediated by different isoforms or homologous proteins.

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Section: Discussionmentioning

confidence: 50%

VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

et al. 2011

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“…The first of these to be identified, VGLUT1, was assigned as a vesicular glutamate transporter after having first been identified as an inorganic phosphate carrier. 358,359 Subsequently, VGLUT2 and VGLUT3 were cloned and characterized and shown to have distinctive distributions in the brain. These transporters have a much lower affinity for glutamate than EAAT1-5 and, unlike the plasma membrane transporters, they do not transport Dand L-aspartate.…”

Section: Vesicular Glutamate Transportersmentioning

confidence: 99%

Molecular Targets for Antiepileptic Drug Development

2007

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Summary:This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the ␣ subunits of voltagegated Na ϩ channels and also T-type voltage-gated Ca 2ϩ channels) or influence GABA-mediated inhibition. Recently, ␣2-␦ voltage-gated Ca 2ϩ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na ϩ channels and GABA A receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca 2ϩ channel subunits and auxiliary proteins, A-or M-type voltage-gated K ϩ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABA B and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits, responsible for hyperpolarization-activated current I h ; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na ϩ channels underlying persistent Na ϩ currents or GABA A receptor isoforms responsible for tonic (extrasynaptic) currents represent attractive targets. The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies.

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“…VGlut1 was previously named the brain, Nadependent Pi (BNPI) transporter because of its homology to inorganic phosphate transporters in the kidney. However, subsequent experimentation established that VGlut1, 2 and 3 are present on vesicular membranes and function as glutamate transporters (Bellocchio et al, 2000;Takamori et al, 2000). By contrast with the plasma membrane glutamate transporters (Eliasof et al, 1998), vesicular glutamate transporters are sodium-independent and exhibit a more than 10-fold lower Km (2 mM: Bellocchio et al, 2000).…”

Section: Vesicular Glutamate Transportersmentioning

confidence: 99%

“…However, subsequent experimentation established that VGlut1, 2 and 3 are present on vesicular membranes and function as glutamate transporters (Bellocchio et al, 2000;Takamori et al, 2000). By contrast with the plasma membrane glutamate transporters (Eliasof et al, 1998), vesicular glutamate transporters are sodium-independent and exhibit a more than 10-fold lower Km (2 mM: Bellocchio et al, 2000). In place of sodium-dependence, glutamate uptake into vesicles relies primarily on the electrical component (ΔΨ) of the electrochemical gradient across the vesicle membrane.…”

Section: Vesicular Glutamate Transportersmentioning

confidence: 99%

“…An interesting property of vesicular glutamate uptake is the presence of a bell-shaped chloride dependence with optimal uptake achieved with low millimolar chloride (Naito and Ueda, 1985;Bellocchio et al, 2000). In rod terminals, E Cl is well above the resting potential and thus the opening of calcium-activated chloride channels or the chloride channels associated with plasma membrane glutamate transporters produces a chloride efflux (Thoreson et al, , 2003aRabl et al, 2003).…”

Section: Vesicular Glutamate Transportersmentioning

confidence: 99%

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Synaptic transmission at retinal ribbon synapses

Heidelberger

Thoreson

Witkovsky

2005

Progress in Retinal and Eye Research

208

231

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The molecular organization of ribbon synapses in photoreceptors and ON bipolar cells is reviewed in relation to the process of neurotransmitter release. The interactions between ribbon synapseassociated proteins, synaptic vesicle fusion machinery and the voltage-gated calcium channels that gate transmitter release at ribbon synapses are discussed in relation to the process of synaptic vesicle exocytosis. We describe structural and mechanistic specializations that permit the ON bipolar cell to release transmitter at a much higher rate than the photoreceptor does, under in vivo conditions. We also consider the modulation of exocytosis at photoreceptor synapses, with an emphasis on the regulation of calcium channels.

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Uptake of Glutamate into Synaptic Vesicles by an Inorganic Phosphate Transporter

Cited by 731 publications

References 43 publications

VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

Molecular Targets for Antiepileptic Drug Development

Synaptic transmission at retinal ribbon synapses

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