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The Journal of Neuroscience, November 1, 1998, 18(21):8648-8659
The Localization of the Brain-Specific Inorganic Phosphate
Transporter Suggests a Specific Presynaptic Role in Glutamatergic
Transmission
Elizabeth E.
Bellocchio1,
Hailan
Hu1,
Alicia
Pohorille2,
June
Chan2,
Virginia M.
Pickel2, and
Robert H.
Edwards1
1 Departments of Neurology and Physiology, Graduate
Programs in Neuroscience and Cell Biology, University of California San
Francisco School of Medicine, San Francisco, California 94143, and
2 Department of Neurology and Neuroscience, Cornell
University Medical College, New York, New York 10021
Molecular cloning has recently identified a vertebrate
brain-specific Na+-dependent inorganic phosphate
transporter (BNPI). BNPI has strong sequence similarity to EAT-4, a
Caenorhabditis elegans protein implicated in
glutamatergic transmission. To characterize the physiological role of
BNPI, we have generated an antibody to the protein. Immunocytochemistry
of rat brain sections shows a light microscopic pattern that is
suggestive of reactivity in nerve terminals. Excitatory projections are
labeled prominently, and ultrastructural analysis confirms that
BNPI localizes almost exclusively to terminals forming asymmetric
excitatory-type synapses. Although BNPI depends on a
Na+ gradient and presumably functions at the plasma
membrane, both electron microscopy and biochemical fractionation show
that BNPI associates preferentially with the membranes of small
synaptic vesicles. The results provide anatomic evidence of a specific presynaptic role for BNPI in glutamatergic neurotransmission, consistent with the phenotype of eat-4 mutants. Because
an enzyme known as the phosphate-activated glutaminase produces
glutamate for release as a neurotransmitter, BNPI may augment
excitatory transmission by increasing cytoplasmic phosphate
concentrations within the nerve terminal and hence increasing glutamate
synthesis. Expression of BNPI on synaptic vesicles suggests a mechanism
for neural activity to regulate the function of BNPI.
Key words:
inorganic phosphate transport; BNPI; synaptic vesicle; asymmetric synapse; excitatory neurotransmission; glutamate release
Copyright © 1998 Society for Neuroscience 0270-6474/98/18218648-12$05.00/0
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