RT Journal Article SR Electronic T1 Identification of the Differentiation-Associated Na+/PI Transporter as a Novel Vesicular Glutamate Transporter Expressed in a Distinct Set of Glutamatergic Synapses JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 142 OP 155 DO 10.1523/JNEUROSCI.22-01-00142.2002 VO 22 IS 1 A1 Hélène Varoqui A1 Martin K.-H. Schäfer A1 Heming Zhu A1 Eberhard Weihe A1 Jeffrey D. Erickson YR 2002 UL http://www.jneurosci.org/content/22/1/142.abstract AB Glutamate transport into synaptic vesicles is a prerequisite for its regulated neurosecretion. Here we functionally identify a second isoform of the vesicular glutamate transporter (VGLUT2) that was previously identified as a plasma membrane Na+-dependent inorganic phosphate transporter (differentiation-associated Na+/PItransporter). Studies using intracellular vesicles from transiently transfected PC12 cells indicate that uptake by VGLUT2 is highly selective for glutamate, is H+ dependent, and requires Cl− ion. Both the vesicular membrane potential (Δψ) and the proton gradient (ΔpH) are important driving forces for vesicular glutamate accumulation under physiological Cl− concentrations. Using an antibody specific for VGLUT2, we also find that this protein is enriched on synaptic vesicles and selective for a distinct class of glutamatergic nerve terminals. The pathway-specific, complementary expression of two different vesicular glutamate transporters suggests functional diversity in the regulation of vesicular release at excitatory synapses. Together, the two isoforms may account for the uptake of glutamate by synaptic vesicles from all central glutamatergic neurons.