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The Journal of Neuroscience, January 1, 2002, 22(1):142-155

Identification of the Differentiation-Associated Na⁺/P_I Transporter as a Novel Vesicular Glutamate Transporter Expressed in a Distinct Set of Glutamatergic Synapses

Hélène Varoqui^{1, 2}, Martin K.-H. Schäfer⁴, Heming Zhu¹, Eberhard Weihe⁴, and Jeffrey D. Erickson^{1, 3}

¹ Neuroscience Center and Departments of ² Opthalmology and ³ Pharmacology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, and ⁴ Department of Molecular Neuroscience, Institute of Anatomy and Cell Biology, Philipps University Marburg, D-35033 Marburg, Germany

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⁺/P_I transporter). 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 () and the proton gradient (pH) 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.

Key words: DNPI; BNPI; VGLUT1; VGLUT2; synaptic vesicle; excitatory synapse; vesicular glutamate transporter; glutamate release; chloride ion; synaptic plasticity; release probability

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Copyright © 2002 Society for Neuroscience  0270-6474/02/221142-14$05.00/0

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