TY - JOUR T1 - The Localization of the Brain-Specific Inorganic Phosphate Transporter Suggests a Specific Presynaptic Role in Glutamatergic Transmission JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8648 LP - 8659 DO - 10.1523/JNEUROSCI.18-21-08648.1998 VL - 18 IS - 21 AU - Elizabeth E. Bellocchio AU - Hailan Hu AU - Alicia Pohorille AU - June Chan AU - Virginia M. Pickel AU - Robert H. Edwards Y1 - 1998/11/01 UR - http://www.jneurosci.org/content/18/21/8648.abstract N2 - Molecular cloning has recently identified a vertebrate brain-specific Na+-dependent inorganic phosphate transporter (BNPI). BNPI has strong sequence similarity to EAT-4, aCaenorhabditis 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. ER -