title: Effective Mechanism for Synthesis of Neurotransmitter Glutamate and its Loading into Synaptic Vesicles.
abstract: Glutamate accumulation into synaptic vesicles is a pivotal step in glutamate transmission. This process is achieved by a vesicular glutamate transporter (VGLUT) coupled to v-type proton ATPase. Normal synaptic transmission, in particular during intensive neuronal firing, would demand rapid transmitter re-filling of emptied synaptic vesicles. We have previously shown that isolated synaptic vesicles are capable of synthesizing glutamate from α-ketoglutarate (not from glutamine) by vesicle-bound aspartate aminotransferase for immediate uptake, in addition to ATP required for uptake by vesicle-bound glycolytic enzymes. This suggests that local synthesis of these substances, essential for glutamate transmission, could occur at the synaptic vesicle. Here we provide evidence that synaptosomes (pinched-off nerve terminals) also accumulate α-ketoglutarate-derived glutamate into synaptic vesicles within, at the expense of ATP generated through glycolysis. Glutamine-derived glutamate is also accumulated into synaptic vesicles in synaptosomes. The underlying mechanism is discussed. It is suggested that local synthesis of both glutamate and ATP at the presynaptic synaptic vesicle would represent an efficient mechanism for swift glutamate loading into synaptic vesicles, supporting maintenance of normal synaptic transmission.
authors: Molecular and Behavioral Neuroscience Institute, Medical School, The University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA.|Department of Education, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo, 156-8502, Japan.
authors: Kouji
authors: K
authors: Takeda
authors: Molecular and Behavioral Neuroscience Institute, Medical School, The University of Michigan, 109 Zina Pitcher Place, Ann Arbor, MI, 48109-2200, USA. tueda@umich.edu.|Department of Pharmacology, Medical School, The University of Michigan, Ann Arbor, MI, 48109, USA. tueda@umich.edu.|Department of Psychiatry, Medical School, The University of Michigan, Ann Arbor, MI, 48109, USA. tueda@umich.edu.
authors: Tetsufumi
authors: T
authors: Ueda
mesh_terms: D000818:Animals; D002417:Cattle; D018698:Glutamic Acid / Q000096:biosynthesis* / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D018377:Neurotransmitter Agents; D018698:Glutamic Acid
keywords: Aspartate aminotransferase; Efficient mechanism; Glutamate; Local synthesis; Synaptic vesicles; VGLUT