The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Metabolic Control of Vesicular Glutamate Transport and Release
Open accessAbstract
Fasting has been used to control epilepsy since antiquity, but the mechanism of coupling between metabolic state and excitatory neurotransmission remains unknown. Previous work has shown that the vesicular glutamate transporters (VGLUTs) required for exocytotic release of glutamate undergo an unusual form of regulation by Cl−. Using functional reconstitution of the purified VGLUTs into proteoliposomes, we now show that Cl− acts as an allosteric activator, and the ketone bodies that increase with fasting inhibit glutamate release by competing with Cl− at the site of allosteric regulation. Consistent with these observations, acetoacetate reduced quantal size at hippocampal synapses, and suppresses glutamate release and seizures evoked with 4-aminopyridine in the brain. The results indicate an unsuspected link between metabolic state and excitatory neurotransmission through anion-dependent regulation of VGLUT activity.
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Cites
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Self-citationVGLUTs define subsets of excitatory neurons and suggest novel roles for glutamate
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Self-citationAstrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate
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Cited by
Suppression of Oxidative Stress by β-Hydroxybutyrate, an Endogenous Histone Deacetylase Inhibitor
Shimazu, T., Hirschey, M. D., Newman, J., He, W., Shirakawa, K., Le Moan, N., Grueter, C. A., Lim, H., Saunders, L. R., Stevens, R. D., et al. (2013) · Science · doi:10.1126/science.1227166 · Cited by 1,777
Ketone bodies as signaling metabolites
Newman, J. C., & Verdin, E. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.09.002 · Cited by 966
β-Hydroxybutyrate: A Signaling Metabolite
Newman, J. C., & Verdin, E. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064916 · Cited by 872
“Cl− is an allosteric activator of glutamate uptake in an in vitro system consisting of proteoliposomes containing purified VGLUT2.”
InfluentialTargeting LDH enzymes with a stiripentol analog to treat epilepsy
Sada, N., Lee, S., Katsu, T., Otsuki, T., & Inoue, T. (2015) · Science · doi:10.1126/science.aaa1299 · Cited by 413
Self-citationFrom glutamate co-release to vesicular synergy: vesicular glutamate transporters
El Mestikawy, S., Wallén-Mackenzie, Å., Fortin, G. M., Descarries, L., & Trudeau, L.-E. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn2969 · Cited by 385
Metadata
- Authors
- Juge, N., Gray, J. A., Omote, H., Miyaji, T., Inoue, T., Hara, C., Uneyama, H., Edwards, R. H., Nicoll, R. A., & Moriyama, Y.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 68
- Issue
- 1
- Pages
- 99-112
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W1993891203
- Cited by
- 400
- References
- 61
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Juge, N., Gray, J. A., Omote, H., Miyaji, T., Inoue, T., Hara, C., Uneyama, H., Edwards, R. H., Nicoll, R. A., & Moriyama, Y. (2010). Metabolic Control of Vesicular Glutamate Transport and Release. Neuron. https://doi.org/10.1016/j.neuron.2010.09.002
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