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Papers In Press, published online ahead of print October 15, 2002
Neuroscience Center/ Pharmacology, LSU Health Sciences Center, New Orleans, LA 70112
Corresponding Author: jerick{at}lsuhsc.edu
We have cloned and functionally characterized a third isoform of a vesicular glutamate transporter (VGLUT3) expressed on synaptic vesicles that identifies a distinct glutamatergic system in the brain that is partly and selectively promiscuous with cholinergic and serotoninergic transmission. Transport activity was specific for glutamate, H+-dependent, stimulated by Cl- ion and inhibited by Rose Bengal and trypan blue. Northern analysis revealed higher mRNA levels in early postnatal development than in adult brain. Restricted patterns of mRNA expression were observed in presumed interneurons in cortex and hippocampus, and projection systems in the lateral and ventrolateral hypothalamic nuclei, limbic system and brainstem. Double in situ hybridization histochemistry for VAChT identified VGLUT3 neurons in striatum as cholinergic interneurons, while VGLUT3 mRNA and protein were absent from all other cholinergic cell groups. In the brain stem VGLUT3 mRNA was concentrated in mesopontine raphé nuclei. VGLUT3-immunoreactivity was present throughout the brain in a diffuse system of thick and thin beaded varicose fibers much less abundant than, and strictly separated from, VGLUT1 or VGLUT2 synapses. Coexistence of VGLUT3 in VMAT2-positive and tyrosine hydroxylase-negative varicosities only in the cerebral cortex and hippocampus and in subsets of tryptophan hydroxylase-positive cell bodies and processes in differentiating primary raphé neurons in vitro indicates selective and target-specific expression of the glutamatergic/serotoninergic synaptic phenotype.
J. Biol. Chem, 10.1074/jbc.M206738200
Submitted on July 8, 2002
Revised on September 23, 2002
Accepted on October 15, 2002
Molecular cloning and functional identification of mouse vesicular glutamate transporter 3 and its expression in subsets of novel excitatory neurons
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