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The Journal of Neuroscience, December 1, 1998, 18(23):9733-9750
The Vesicular GABA Transporter, VGAT, Localizes to Synaptic
Vesicles in Sets of Glycinergic as Well as GABAergic Neurons
Farrukh A.
Chaudhry1, 2,
Richard J.
Reimer2,
Elizabeth E.
Bellocchio2,
Niels C.
Danbolt1,
Kirsten
K.
Osen1,
Robert H.
Edwards2, and
Jon
Storm-Mathisen1
1 Department of Anatomy, Institute of Basic Medical
Sciences, University of Oslo, N-0317 Oslo, Norway, and
2 Departments of Neurology and Physiology, University of
California San Francisco School of Medicine, San Francisco, California
94143-0435
A transporter thought to mediate accumulation of GABA into
synaptic vesicles has recently been cloned (). This vesicular GABA transporter (VGAT), the first vesicular amino acid
transporter to be molecularly identified, differs in structure from
previously cloned vesicular neurotransmitter transporters and defines a
novel gene family. Here we use antibodies specific for N- and
C-terminal epitopes of VGAT to localize the protein in the rat
CNS. VGAT is highly concentrated in the nerve endings of
GABAergic neurons in the brain and spinal cord but also in glycinergic
nerve endings. In contrast, hippocampal mossy fiber boutons, which
although glutamatergic are known to contain GABA, lack VGAT
immunoreactivity. Post-embedding immunogold quantification shows that
the protein specifically associates with synaptic vesicles. Triple
labeling for VGAT, GABA, and glycine in the lateral oliva superior
revealed a higher expression of VGAT in nerve endings rich in GABA,
with or without glycine, than in others rich in glycine only. Although
the great majority of nerve terminals containing GABA or glycine are
immunopositive for VGAT, subpopulations of nerve endings rich in GABA
or glycine appear to lack the protein. Additional vesicular
transporters or alternative modes of release may therefore contribute
to the inhibitory neurotransmission mediated by these two amino acids.
Key words:
neurotransmitter transport; synaptic vesicles; GABA; glycine; antibodies; immunogold; microscopy
Copyright © 1998 Society for Neuroscience 0270-6474/98/18239733-18$05.00/0
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