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Synaptic vesicles are capable of synthesizing the VGLUT substrate glutamate from α‐ketoglutarate for vesicular loading
Author(s) -
Takeda Kouji,
Ishida Atsuhiko,
Takahashi Kento,
Ueda Tetsufumi
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07684.x
Subject(s) - glutamate receptor , synaptic vesicle , vesicle , glutamate aspartate transporter , neurotransmission , biochemistry , biophysics , atpase , biology , chemistry , neuroscience , microbiology and biotechnology , enzyme , metabotropic glutamate receptor , membrane , receptor
J. Neurochem. (2012) 121 , 184–196. Abstract Synaptic 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.