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Synaptic vesicles are capable of synthesizing the VGLUT substrate glutamate from α‐ketoglutarate for vesicular loading
dc.contributor.authorTakeda, Koujien_US
dc.contributor.authorIshida, Atsuhikoen_US
dc.contributor.authorTakahashi, Kentoen_US
dc.contributor.authorUeda, Tetsufumien_US
dc.date.accessioned2012-05-21T15:49:34Z
dc.date.available2013-06-11T19:15:53Zen_US
dc.date.issued2012-04en_US
dc.identifier.citationTakeda, Kouji; Ishida, Atsuhiko; Takahashi, Kento; Ueda, Tetsufumi (2012). "Synaptic vesicles are capable of synthesizing the VGLUT substrate glutamate from α‐ketoglutarate for vesicular loading." Journal of Neurochemistry 121(2). <http://hdl.handle.net/2027.42/91212>en_US
dc.identifier.issn0022-3042en_US
dc.identifier.issn1471-4159en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/91212
dc.description.abstractSynaptic vesicle loading of glutamate is a pivotal step in glutamate synaptic transmission. The molecular machinery responsible for this step is comprised of v‐type proton‐pump ATPase and a vesicular glutamate transporter. Recent evidence indicates that synaptic vesicles are endowed with glycolytic ATP‐synthesizing enzymes, providing energy for immediate use by vesicle‐bound proton‐pump ATPase. In this study, we provide evidence that synaptic vesicles are also capable of synthesizing the vesicular glutamate transporter substrate glutamate, from α‐ketoglutarate and l ‐aspartate (as the amino group donor); glutamate thus produced is taken up into vesicles. We also report a finding that α‐ketoglutarate‐derived glutamate uptake into synaptic vesicles and aspartate aminotransferase are inhibited by 2,3‐pyrazinedicarboxylate. Evidence is given that this is a selective inhibitor for aspartate aminotransferase. These observations provide insight into understanding the nerve endings’ mechanism for high efficiency in glutamate transmission. Finding this inhibitor may have implications for further experimentation on the role of α‐ketoglutarate‐derived glutamate in glutamate transmission. Synaptic vesicle loading of glutamate is the first step in glutamate synaptic transmission. We provide evidence that the VGLUT substrate glutamate is locally synthesized on the surface of vesicles from α‐ketoglutarate and aspartate by aspartate aminotransferase, and taken up into vesicles, indicating high efficiency in glutamate transmission. We have also found that 2,3‐pyrazinedicarboxylate inhibits this synthetic enzyme. Finding this inhibitor has important implications for defining the role of vesicle‐bound aspartate aminotransferase in glutamate transmission.en_US
dc.publisherWiley Periodicals, Inc.en_US
dc.publisherBlackwell Publishing Ltden_US
dc.subject.otherGOTen_US
dc.subject.otherNeurotransmitteren_US
dc.subject.otherPrecursoren_US
dc.subject.otherBiosynthesisen_US
dc.subject.otherLocal Synthesisen_US
dc.titleSynaptic vesicles are capable of synthesizing the VGLUT substrate glutamate from α‐ketoglutarate for vesicular loadingen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelNeurosciencesen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDepartment of Pharmacology, Medical School, The University of Michigan, Ann Arbor, Michigan, USAen_US
dc.contributor.affiliationumMolecular & Behavioral Neuroscience Institute, Medical School, The University of Michigan, Ann Arbor, Michigan, USAen_US
dc.contributor.affiliationumDepartment of Psychiatry, Medical School, The University of Michigan, Ann Arbor, Michigan, USAen_US
dc.contributor.affiliationotherLaboratory of Molecular Brain Science, Graduate School of Integrated Arts and Sciences, Hiroshima University, Higashi‐Hiroshima, Japanen_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/91212/1/j.1471-4159.2012.07684.x.pdf
dc.identifier.doi10.1111/j.1471-4159.2012.07684.xen_US
dc.identifier.sourceJournal of Neurochemistryen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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